当前期刊: BMC Complementary and Alternative Medicine Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Cordyceps militaris induces apoptosis in ovarian cancer cells through TNF-α/TNFR1-mediated inhibition of NF-κB phosphorylation
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Eunbi Jo; Hyun-Jin Jang; Kyeong Eun Yang; Min Su Jang; Yang Hoon Huh; Hwa-Seung Yoo; Jun Soo Park; Ik-Soon Jang; Soo Jung Park

    Cordyceps militaris (L.) Fr. (C. militaris) exhibits pharmacological activities, including antitumor properties, through the regulation of the nuclear factor kappa B (NF-κB) signaling. Tumor Necrosis Factor (TNF) and TNF-α modulates cell survival and apoptosis through NF- κB signaling. However, the mechanism underlying its mode of action on the NF-κB pathway is unclear. Here, we analyzed the effect of C. militaris extract (CME) on the proliferation of ovarian cancer cells by confirming viability, morphological changes, migration assay. Additionally, CME induced apoptosis was determined by apoptosis assay and apoptotic body formation under TEM. The mechanisms of CME were determined through microarray, immunoblotting and immunocytochemistry. CME reduced the viability of cells in a dose-dependent manner and induced morphological changes. We confirmed the decrease in the migration activity of SKOV-3 cells after treatment with CME and the consequent induction of apoptosis. Immunoblotting results showed that the CME-mediated upregulation of tumor necrosis factor receptor 1 (TNFR1) expression induced apoptosis of SKOV-3 cells via the serial activation of caspases. Moreover, CME negatively modulated NF-κB activation via TNFR expression, suggestive of the activation of the extrinsic apoptotic pathway. The binding of TNF-α to TNFR results in the disassociation of IκB from NF-κB and the subsequent translocation of the active NF-κB to the nucleus. CME clearly suppressed NF-κB translocation induced by interleukin (IL-1β) from the cytosol into the nucleus. The decrease in the expression levels of B cell lymphoma (Bcl)-xL and Bcl-2 led to a marked increase in cell apoptosis. These results suggest that C. militaris inhibited ovarian cancer cell proliferation, survival, and migration, possibly through the coordination between TNF-α/TNFR1 signaling and NF-κB activation. Taken together, our findings provide a new insight into a novel treatment strategy for ovarian cancer using C. militaris.

    更新日期:2020-01-16
  • Acute and sub-acute toxicity of Echinops kebericho decoction in rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Serawit Deyno; Abiy Abebe; Mesfin Asefa Tola; Ariya Hymete; Joel Bazira; Eyasu Makonnen; Paul E. Alele

    Echinops kebericho is widely used for treatment of a variety of diseases including infectious, non-infectious disease and fumigation during child birth. Antibacterial, antimalarial, anti-leshimania, anti-diarrheal and insect repellent activities have been elucidated. Its toxicity profile is not yet investigated and thus this study was to investigate acute and sub-acute toxicity of E. kebericho decoctions. Acute toxicity study was performed in female Wistar albino rats with single oral dose and followed up to 14 days. The sub-acute oral dose toxicity studies were conducted in rats of both sexes in accordance with the repeated dose 28-day oral toxicity study in rodent OECD guidelines. Physical observations were made regularly during the study period while body weight was measured weekly. Organ weight, histopathology, clinical chemistry and hematology data were collected on the 29th day. Results were presented as mean ± standard deviation. One-way analysis of variance (ANOVA) was performed if assumptions were met; otherwise Kruskal-Wallis analysis was performed. Oral administration of E. kebericho decoction showed no treatment-related mortality in female rats up to the dose of 5000 mg/kg. In sub-acute toxicity studies, no significant treatment-related abnormalities were observed compared to negative controls. Food consumption, body weight, organ weight, hematology, clinical chemistry, and histopathology did not show significant variation between controls and treatment groups. However, creatinine, relative lung weight, triglycerides, and monocytes were lower in treated compared to control groups. Significant variations between male and female groups in food consumption, relative organ weight, hematology, clinical chemistry were observed. Histolo-pathology of high-dose treated groups showed fatty liver. Echinops kebericho showed LD50 of greater than 5000 mg/kg in acute toxicity study and is well tolerated up to the dose of 600 mg/kg body weight in sub-acute toxicity study.

    更新日期:2020-01-16
  • Xiao-ai-ping injection adjunct with platinum-based chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Fanchao Feng; Jingyi Huang; Zhichao Wang; Jiarui Zhang; Di Han; Qi Wu; Hailang He; Xianmei Zhou

    Xiao-ai-ping injection (XAPI), as patented Chinese medicine, has shown promising outcomes in non-small-cell lung cancer (NSCLC) patients. This meta-analysis investigated the efficacy and safety of XAPI in combination with platinum-based chemotherapy. A comprehensive literature search was conducted to identify relevant studies in Pubmed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Wangfang Database, VIP Database, and Chinese Biology Medical Database from the date of their inception to September 2018. The RevMan 5.3 software was applied to calculate the risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI). We included and analyzed 24 randomized controlled trials. The meta-analysis showed that XAPI adjunctive to platinum-based chemotherapy had better outcomes in objective tumor response rate (ORR) (RR: 1.27, 95% CI, 1.14–1.40); improved Karnofsky performance scores (KPS) (RR: 1.70, 95% CI, 1.48–1.95); reduction in occurrence of grade 3/4 leukopenia (RR: 0.49, 95% CI, 0.38–0.64), anemia (RR: 0.63, 95% CI, 0.46–0.87) and thrombocytopenia (RR: 0.53, 95% CI, 0.38–0.73), nausea and vomiting (RR: 0.57, 95% CI, 0.36–0.90); and enhanced immune function (CD8+ [MD: 4.96, 95% CI, 1.16–8.76] and CD4+/CD8+ [MD: 2.58, 95% CI, 1.69–3.47]). However, it did not increase dysregulated liver and kidney function, diarrhea, constipation, and fatigue. Subgroup analysis of ORR and KPS revealed that dosage, treatment duration, and methodological quality did not affect the outcome significantly. Our meta-analyses demonstrated that XAPI in combination with platinum-based chemotherapy had a better tumor response, improved the quality of life, attenuated adverse side effects, and enhanced immune function, which suggests that it might be used for advanced NSCLC. Moreover, low dosage (< 60 ml/d) and long-term treatment of XAPI might be a choice for advanced NSCLC patients.

    更新日期:2020-01-16
  • Parents’ experiences of information-seeking and decision-making regarding complementary medicine for children with autism spectrum disorder: a qualitative study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Caroline A. Smith; Chloe Parton; Marlee King; Gisselle Gallego

    Complementary and alternative medicine and therapies (CAM) are widely used by parents of children with autism spectrum disorder (ASD). However, there is a gap in our understanding of how and why parents of children with ASD make decisions about CAM treatment, and how “evidence” influences their decision-making. The aim of this study was to explore views and perspectives on CAM decision-making among parents of children with ASD in Australia. Semi-structured interviews were conducted with parents of children with ASD (18 years and under) who were living in Australia. The interviews were digitally recorded, transcribed and then analysed using thematic analysis. Twenty-one parents were interviewed (20 women and one man). The mean age of participants was 43 years, (SD = 5.12 years), the majority of whom were born in Australia (71%), and almost half (43%) had a bachelor degree or higher. Three main themes were identifiedin the thematic analysis. First theme was ‘Parents’ experiences of researching CAM treatments, the second theme was, “Navigating CAM information and practices”, which comprises of the subthemes: Assessing information on CAM treatments’ What counts as ‘evidence’? and Assessing the impact of CAM treatments on the child - What counts as effective?, and the final theme was, “Creating a central and trustworthy source about CAM”. Across themes parents’ CAM decision-making was described as pragmatic, influenced by time, cost, and feasibility. Parents also reported that information on CAM was complex and often conflicting, and the creation of a centralised and reliable source of information on CAM was identified as a potential solution to these challenges. The development of evidence-based information resources for parents and supporting CAM health literacy may assist with navigating CAM decision-making for children’s with ASD.

    更新日期:2020-01-16
  • Antiproliferative and apoptotic effects of proteins from black seeds (Nigella sativa) on human breast MCF-7 cancer cell line
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-13
    Yamna Khurshid; Basir Syed; Shabana U. Simjee; Obaid Beg; Aftab Ahmed

    Nigella sativa (NS), a member of family Ranunculaceae is commonly known as black seed or kalonji. It has been well studied for its therapeutic role in various diseases, particularly cancer. Literature is full of bioactive compounds from NS seed. However, fewer studies have been reported on the pharmacological activity of proteins. The current study was designed to evaluate the anticancer property of NS seed proteins on the MCF-7 cell line. NS seed extract was prepared in phosphate-buffered saline (PBS), and proteins were precipitated using 80% ammonium sulfate. The crude seed proteins were partially purified using gel filtration chromatography, and peaks were resolved by SDS-PAGE. MTT assay was used to screen the crude proteins and peaks for their cytotoxic effects on MCF-7 cell line. Active Peaks (P1 and P4) were further studied for their role in modulating the expression of genes associated with apoptosis by real-time reverse transcription PCR. For protein identification, proteins were digested, separated, and analyzed with LC-MS/MS. Data analysis was performed using online Mascot, ExPASy ProtParam, and UniProt Knowledgebase (UniProtKB) gene ontology (GO) bioinformatics tools. Gel filtration chromatography separated seed proteins into seven peaks, and SDS-PAGE profile revealed the presence of multiple protein bands. Among all test samples, P1 and P4 depicted potent dose-dependent inhibitory effect on MCF-7 cells exhibiting IC50 values of 14.25 ± 0.84 and 8.05 ± 0.22 μg/ml, respectively. Gene expression analysis demonstrated apoptosis as a possible cell killing mechanism. A total of 11 and 24 proteins were identified in P1 and P4, respectively. The majority of the proteins identified are located in the cytosol, associate with biological metabolic processes, and their molecular functions are binding and catalysis. Hydropathicity values were mostly in the hydrophilic range. Our findings suggest NS seed proteins as a potential therapeutic agent for cancer. To our knowledge, it is the first study to report the anticancer property of NS seed proteins.

    更新日期:2020-01-16
  • Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Wei Zhou; Jiarui Wu; Yingli Zhu; Ziqi Meng; Xinkui Liu; Shuyu Liu; Mengwei Ni; Shanshan Jia; Jingyuan Zhang; Siyu Guo

    As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out. In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo. This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

    更新日期:2020-01-16
  • Comparison of the acute toxicity, analgesic and anti-inflammatory activities and chemical composition changes in Rhizoma anemones Raddeanae caused by vinegar processing
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Sha-Sha Wang; Shao-Yan Zhou; Xiao-Yan Xie; Ling Zhao; Yao Fu; Guang-Zhi Cai; Ji-Yu Gong

    As the dry rhizome of Anemone raddeana Regel, Rhizoma Anemones Raddeanae (RAR), which belongs to Ranunculaceae, is usually used to treat wind and cold symptoms, hand-foot disease and spasms, joint pain and ulcer pain in China. It is well known that the efficacy of RAR can be distinctly enhanced by processing with vinegar due to the reduced toxicity and side effects. However, the entry of vinegar into liver channels can cause a series of problems. In this paper, the differences in the acute toxicity, anti-inflammatory and analgesic effects between RAR and vinegar-processed RAR were compared in detail. The changes in the chemical compositions between RAR and vinegar-processed RAR were investigated, and the mechanism of vinegar processing was also explored. Acute toxicity experiments were used to examine the toxicity of vinegar-processed RAR. A series of studies, such as the writhing reaction, ear swelling experiment, complete Freund’s adjuvant-induced rat foot swelling experiment and cotton granuloma, in experimental mice was conducted to observe the anti-inflammatory effect of vinegar-processed RAR. The inflammatory cytokines of model rats were determined by enzyme-linked immunosorbent assay (ELISA). Liquid Chromatography-Quadrupole-Time of Flight mass spectrometer Detector (LC-Q-TOF) was used to analyse the chemical compositions of the RARs before and after vinegar processing. Neither obvious changes in mice nor death phenomena were observed as the amount of vinegar-processed RAR in crude drug was set at 2.1 g/kg. Vinegar-processed RAR could significantly prolong the latency, reduce the writhing reaction time to reduce the severity of ear swelling and foot swelling, and remarkably inhibit the secretion of Interleukin-1β(IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) proinflammatory cytokines. The content of twelve saponins (e.g., Eleutheroside K) in RAR was decreased after vinegar processing, but six other types (e.g., RDA) were increased. These results revealed that vinegar processing could not only improve the analgesic and anti-inflammatory effects of RAR but also reduce its own toxicity. Not applicable.

    更新日期:2020-01-16
  • Cytotoxycity and antiplasmodial activity of phenolic derivatives from Albizia zygia (DC.) J.F. Macbr. (Mimosaceae)
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Romeol Romain Koagne; Frederick Annang; Bastien Cautain; Jesús Martín; Guiomar Pérez-Moreno; Gabin Thierry M. Bitchagno; Dolores González-Pacanowska; Francisca Vicente; Ingrid Konga Simo; Fernando Reyes; Pierre Tane

    The proliferation and resistance of microorganisms area serious threat against humankind and the search for new therapeutics is needed. The present report describes the antiplasmodial and anticancer activities of samples isolated from the methanol extract of Albizia zygia (Mimosaseae). The plant extract was prepared by maceration in methanol. Standard chromatographic, HPLC and spectroscopic methods were used to isolate and identify six compounds (1–6). The acetylated derivatives (7–10) were prepared by modifying 2-O-β-D-glucopyranosyl-4-hydroxyphenylacetic acid and quercetin 3-O-α-L-rhamnopyranoside, previously isolated from A. zygia (Mimosaceae). A two-fold serial micro-dilution method was used to determine the IC50s against five tumor cell lines and Plasmodium falciparum. In general, compounds showed moderate activity against the human pancreatic carcinoma cell line MiaPaca-2 (10 < IC50 < 20 μM) and weak activity against other tumor cell lines such as lung (A-549), hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7and A2058) (IC50 > 20 μM). Additionally, the two semi-synthetic derivatives of quercetin 3-O-α-L-rhamnopyranoside exhibited significant activity against P. falciparum with IC50 of 7.47 ± 0.25 μM for compound 9 and 6.77 ± 0.25 μM for compound 10, higher than that of their natural precursor (IC50 25.1 ± 0.25 μM). The results of this study clearly suggest that, the appropriate introduction of acetyl groups into some flavonoids could lead to more useful derivatives for the development of an antiplasmodial agent.

    更新日期:2020-01-16
  • Toxicology studies of aqueous-alcohol extracts of Harpagophytum procumbens subsp. procumbens (Burch.) DC.Ex Meisn. (Pedaliaceae) in female and male rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Kirtan Joshi; Alan Parrish; Elizabeth A. Grunz-Borgmann; Mary Gerkovich; William R. Folk

    A variety of medicinal products prepared from secondary tubers of Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn. (Devil’s Claw) and H. zeyheri are marketed in Africa, Europe, the United States, South America and elsewhere, where they are used for inflammatory and musculoskeletal conditions such as arthritis, lower back pain, rheumatism and neuralgia, etc. While clinical studies conducted over the last twenty years support the general safety of such products, infrequent gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), headache, vertigo and hypersensitivity (allergic) reactions (rash, hives and face swelling) have been documented. Sex-related differences occur in the health conditions for which Devil’s Claw products are used, so it is likely that usage is similarly sex-related and so might be side effects and potential toxicities. However toxicologic studies of Devil’s Claw products have been conducted primarily with male animals. To address this deficit, we report toxicological studies in female and male rats of several H. procumbens (HP) aqueous-alcohol extracts chemically analyzed by UPLC-MS. Female and male Sprague Dawley rats were studied for one and three months in groups differing by consumption of diets without and with HP extracts at a 7–10-fold human equivalent dose (HED). Sera were analyzed for blood chemistry, and heart, liver, lung, kidney, stomach, and small and large intestine tissues were examined for histopathology. Treatment group differences for blood chemistry were analyzed by ANOVA with Dunnett’s test and significant group differences for endpoints with marginal distributional properties were verified using the Kruskal-Wallis test. Group differences for histopathology were tested using Chi Square analysis. Significant group by sex-related differences in blood chemistry were detected in both studies. Additionally, several sex-related differences occurred between the studies. However, significant histopathology effects associated with the consumption of the extracts were not detected. Toxicologic analysis of Devil’s Claw extracts cause significant sex-related effects in blood chemistry. However, in our judgement, none of the observed effects suggest serious toxicity at these doses and durations. Subsequent toxicologic and clinical studies of H. procumbens and other medicines with similar properties should explore in greater detail the basis and consequences of potential sex-related effects.

    更新日期:2020-01-16
  • Expert consensus on the development of a health-related questionnaire for the pediatric field of Korean medicine: a Delphi study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Jihong Lee; Sun Haeng Lee; Gyu Tae Chang

    Although a variety of patient-reported outcome measures (PROMs) for children have been developed, there is no pediatric PROM specific to Korean medicine (KM) that is validated by experts in the field. The aim of this study was to collate the opinions of specialists in KM pediatrics on the development of a generic PROM that can be used by Korean medical doctors to assess the health status of children. A three-round Delphi survey was conducted to determine the level of consensus on the development of a new PROM. Delphi questionnaires were sent by e-mail to 91 KM pediatricians on January 24, 2018. The Delphi questionnaire was composed of four sections: conceptualization, construction, items, and sources of content for a PROM. A nine-point Likert scale was used, and if more than two-thirds of the panels agreed or disagreed with a given sentence, they were considered to have reached a consensus. A draft of a PROM for the pediatric field of KM was developed in accordance with the preliminary conceptual framework. Out of 91 experts, 18 finished three rounds of the Delphi survey. The experts reached a consensus on the necessity of a KM pediatric PROM for measuring various areas including child health, and using Likert scales with a recall period of 3 months. They also agreed on specific items and sources of content. A new draft of a health questionnaire for KM pediatrics was developed based on the Delphi consensus. It contains 44 items covering 7 domains: i) functions of the digestive system, ii) functions of the respiratory system, iii) mental functions, iv) skin functions, v) pain, vi) functions of the metabolic and endocrine systems, and vii) demographic details. This research represents the first step in developing a health questionnaire for the pediatric field of KM. The questionnaire can be used in clinical and research settings after verifying several types of validity and reliability.

    更新日期:2020-01-16
  • Ginsenoside Rb1 can ameliorate the key inflammatory cytokines TNF-α and IL-6 in a cancer cachexia mouse model
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Shuai Lu; Yubo Zhang; Huajun Li; Jing Zhang; Yingqian Ci; Mei Han

    Cancer cachexia is a severe condition that leads to the death of advanced cancer patients, and approximately 50~80% of cancer patients have cancer cachexia. Ginseng extract has been reported to have substantial anticancer and immune-enhancing effects; however, no study has reported the use of ginseng alone to treat cancer cachexia. Our study’s purpose was to investigate the therapeutic effects of ginseng-related monomers or mixtures on a cancer cachexia mouse model. We selected BALB/c mice and injected the mice subcutaneously with C26 colon cancer cells to construct a cancer cachexia experimental animal model. The water extract of ginseng (WEG), two types of ginseng extracts (ginsenosides at doses of 5 mg/kg (GE5) and 50 mg/kg (GE50)) and ginsenoside Rb1 (Rb1) were used to treat cancer cachexia mice. Enzyme-linked immunosorbent assays (ELISAs) were used to analyze the inhibitory effects on two key inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Our experimental results show that GE5, GE50 and Rb1 significantly reduced the levels of TNF-α (P < 0.01) and IL-6 (P < 0.01), which are closely related to cancer cachexia; however, WEG, GE5, GE50 and Rb1 did not significantly improve the gastrocnemius muscle weight or the epididymal fat weight of mice with cancer cachexia. These results indicate that GE5, GE50 and Rb1 may be useful for reducing symptoms due to inflammation by reducing the TNF-α and IL-6 cytokine levels in cancer cachexia mice, thereby ameliorating the symptoms of cancer cachexia. Our results may be beneficial for future studies on the use of Chinese herbal medicines to treat cancer cachexia.

    更新日期:2020-01-16
  • Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Nadia Montero-Oleas; Ingrid Arevalo-Rodriguez; Solange Nuñez-González; Andrés Viteri-García; Daniel Simancas-Racines

    Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps. We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios. A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores. Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

    更新日期:2020-01-16
  • Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-15
    Zi-fei Yin; Yang-lin Wei; Xuan Wang; Li-na Wang; Xia Li

    Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro. TGF-β1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot. BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-β1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-β1 stimulated A549 cells. These results indicate that BYHWT suppressed TGF-β1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.

    更新日期:2020-01-16
  • The use of Euphorbia hirta L. (Euphorbiaceae) in diarrhea and constipation involves calcium antagonism and cholinergic mechanisms
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-16
    Muhammad Zeeshan Ali; Malik Hassan Mehmood; Muhammad Saleem; Anwarul-Hassan Gilani

    Euphorbia hirta (Linn) family Euphorbiaceae has been used in indigenous system of medicine for the treatment of gastrointestinal disorders. This study was designed to determine the pharmacological basis for the medicinal use of E. hirta in diarrhea and constipation. The aqueous-methanol extract of whole herb of E. hirta (EH.Cr) and its petroleum ether (Pet.EH), chloroform (CHCl3.EH), ethyl acetate (Et.Ac.EH) and aqueous (Aq.EH) fractions were tested in the in-vivo experiments using Balb/c mice, while the in-vitro studies were performed on isolated jejunum and ileum preparations of locally bred rabbit and Sprague Dawley rats, respectively, using PowerLab data system. Qualitative phytochemical analysis showed the presence of alkaloids, saponins, flavonoids, tannins, phenols, cardiac glycosides, while HPLC of EH.Cr showed quercetin in high proportion. In mice, EH.Cr at the dose of 500 and 1000 mg/kg showed 41 and 70% protection from castor oil-induced diarrhea, respectively, similar to the effect of quercetin and loperamide, while at lower doses (50 and 100 mg/kg), it caused an increase in the fecal output. In loperamide-induced constipated mice, EH.Cr also displayed laxative effect with respective values of 28.6 and 35.3% at 50 and 100 mg/kg. In rabbit jejunum, EH.Cr showed atropine-sensitive inhibitory effect in a concentration-dependent manner, while quercetin and nifedipine exhibited atropine-insensitive effects. Fractions of E. hirta also produced atropine-sensitive inhibitory effects except Pet.EH and CHCl3.EH. On high (80 mM) and low (20 mM) K+ − induced contractions, the crude extract and fractions exhibited a concentration-dependent non-specific inhibition of both spasmogens and displaced concentration-response curves of Ca++ to the right with suppression of the maximum effect similar to the effect quercetin and nifedipine. Fractions showed wide distribution of spasmolytic and Ca++ antagonist like effects. In rat ileum, EH.Cr and its fractions exhibited atropine-sensitive gut stimulant effects except Pet.EH. The crude extract of E. hirta possesses antidiarrheal effect possibly mediated through Ca++ antagonist like gut inhibitory constituents, while its laxative effect was mediated primarily through muscarinic receptor agonist like gut stimulant constituents. Thus, these findings provide an evidence to the folkloric use of E. hirta in diarrhea and constipation.

    更新日期:2020-01-16
  • The effects of add-on self-care education on quality of life and fatigue in gastrointestinal cancer patients undergoing chemotherapy
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2020-01-16
    Jun Xie; Tingli Zhu; Qun Lu; Xiaomin Xu; Yinghua Cai; Zhenghong Xu

    Gastrointestinal cancer is one of the most common malignancies and imposes heavy burdens on both individual health and social economy. We sought to survey the effect of a self-care education program on quality of life and fatigue in gastrointestinal cancer patients who received chemotherapy. Ninety-one eligible gastrointestinal cancer patients were enrolled in this study and 86 valid samples were analyzed. Data were acquired with a demographics questionnaire, endpoint multidimensional questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30. The collected data were analyzed using SPSS software. The self-care education intervention significantly improved the quality of life with respect to emotional function (p = 0.018), role function (p = 0.041), cognitive function (p = 0.038) and alleviated side effects such as nausea/vomiting (p = 0.028) and fatigue (p = 0.029). Further analysis demonstrated that the self-care education benefited total fatigue, affective fatigue and cognitive fatigue in gastrointestinal cancer patients regardless of baseline depression. Our results suggested the beneficial effects of the self-care education in both quality of life and anti-fatigue in gastrointestinal cancer patients under chemotherapy. The self-care education could be considered as a complementary approach during combination chemotherapy in gastrointestinal cancer patients.

    更新日期:2020-01-16
  • Complementary medicine use among Australian patients in an acute hospital setting: an exploratory, cross sectional study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-21
    Freya Waddington; Jenny Lee; Mark Naunton; Greg Kyle; Jackson Thomas; Gabrielle O’Kane

    The use of Complementary Medicines (CMs) has significantly increased in Australia over the last decade. This study attempts to determine the extent to which complementary and alternative medicines are recorded, ceased or initiated in the acute hospital setting and investigate which health professionals have a role in this process. A cross-sectional study of inpatients was conducted at a major tertiary teaching hospital. Patient’s medical records were examined to determine the rates of complementary medicine (CM) use and recording on medication charts and discharge prescriptions. Patient progress notes were audited to determine which health professionals were involved with the initiation or cessation of CMs during the inpatient stay. Three hundred and forty-one patients were included for analysis of which 44.3% (n = 151) participants were recorded as utilizing a CM. Patients were admitted on a mean of 2 (±1.4[Sd]; 0–9[range]) CMs and discharged on a mean of 1.7 CMs (±1.3[Sd]; 0–5[range]). 274 individual CMs were recorded on inpatient medication reconciliation forms with multivitamins, magnesium, fish oil and cholecalciferol recorded the most frequently. One hundred and fifty-eight changes to patient CM usage were recorded during the patient hospitalisation. One hundred and seven of these changes (68%) were not accounted for in the patient progress notes. Patients use of CM in this hospital setting do not reflect the national estimated usage. On the occasions that CM products are included in patient records, they are subsequently deprescribed following patient examination in hospital. It is currently unclear which health professionals have a role in this deprescribing process.

    更新日期:2019-12-22
  • Anti-inflammatory, analgesic and acute toxicity effects of fermented soybean
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-19
    Hamidah Mohd Yusof; Norlaily Mohd Ali; Swee Keong Yeap; Wan Yong Ho; Boon Kee Beh; Soo Peng Koh; Kamariah Long; Noorjahan Banu Alitheen

    Tempeh is a widely known fermented soybean that contains elevated level of bioactive contents. Our previous study has shown that anaerobic fermented Nutrient Enriched Soybean Tempeh (NESTE) with increase amino acid and antioxidant levels possessed better hepatoprotective effect than raw soybean. In this study, the anti-inflammatory effect of the NESTE aqueous extract and raw soybean aqueous extract (SBE) were evaluated by quantifying the inhibition of IL-1β, TNF-α and nitric oxide (NO) secretion in LPS treated RAW 264.7 cell in vitro. On the other hand, in vivo oral acute toxicity effect of the extract was tested on mice at the dose of 5000 mg/kg body weight. In vivo oral analgesic effect of both aqueous extracts at 200 and 1000 mg/kg body weight was evaluated by the hot plate test. In the in vitro anti-inflammatory study, 5 mg/mL NESTE was able to inhibit 25.50 ± 2.20%, 35.88 ± 3.20% and 28.50 ± 3.50% of NO, IL-1β and TNF-α production in LPS treated RAW 264.7 cells without inducing cytotoxic effect on the cells. However, this effect was lower than 4 μg/mL of curcumin, which inhibited NO, IL-1β and TNF-α production by 89.50 ± 5.00%, 78.80 ± 6.20% and 87.30 ± 4.00%, respectively. In addition, 1.5 to 2.5-fold increase of latency period up to 120 min for mice in the hot plate test was achieved by 1000 mg/kg NESTE. The analgesic effect of NESTE was better than 400 mg/kg of acetyl salicylic acid, which only increased ~ 1.7-fold of latency period up to 90 min. Moreover, NESTE did not show acute toxicity (no LD50) up to 5000 mg/kg body weight. NESTE is a nutritious food ingredient with potential anti-inflammatory and analgesic effects.

    更新日期:2019-12-19
  • Alcohol extract from Vernonia anthelmintica willd (L.) seed counteracts stress-induced murine hair follicle growth inhibition
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-17
    Qian Wang; Yongxin Wang; Silin Pang; Jia Zhou; Jie Cai; Jing Shang

    Vernonia anthelmintica (L.) willd is a traditional urgur herb in China for a long history. Its alcohol extract (AVE) has been proved to promote hair follicle growth in C57BL/6 mice. We conducted this study to investigate the hair-growth effects of AVE in stressed mice and its possible mechanism of action. The hair-follicle growth effects of AVE were examined by in vivo and in vitro study. We exposed C57BL/6 male mice to chronic restraint stress to induce murine hair follicle growth inhibition. The effects of AVE were examined by histological analysis, immunofluorescence for Ki67 and cytokeratin 19 immunoreactivity, western blot assay in tyrosinase and related proteins expressions and immunofluorescence for nerve fibers. In organ culture of mouse vibrissae follicles, we used substance P as a catagen-inducing factor of hair follicle growth, and measured the elongation of hair shafts and expression of neurokinin-1 receptor protein by application of AVE. Our results showed that AVE counteract murine hair follicle growth inhibition caused by chronic restraint stress via inducing the conversion of telogen to anagen and inhibiting catagen premature, increasing bulb keratinocytes and bulge stem cells proliferation, promoting melanogenesis, and reducing the numbers of substance P and calcitonin gene-related peptide nerve fibers. Furthermore, AVE also counteracted murine hair follicle growth inhibition caused by substance P in organ culture. These results suggest that AVE counteract stress-induced hair follicle growth inhibition in C57BL/6 mice in vivo and in vitro, and may be an effective new candidate for treatment of stress-induced hair loss.

    更新日期:2019-12-18
  • Helminthostachys zeylanica alleviates hepatic steatosis and insulin resistance in diet-induced obese mice
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-13
    Ting-Chen Chang; Hao Chiang; Yu-Heng Lai; Yu-Ling Huang; Hsiu-Chen Huang; Yu-Chih Liang; Hui-Kang Liu; Cheng Huang

    Obesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems. It has been shown that insulin resistance is associated with increased hepatic lipid and causes hepatic steatosis through a myriad of mechanisms, including inflammatory signaling. Helminthostachys zeylanica (HZ) is used widely as a common herbal medicine to relieve fever symptoms and inflammatory diseases in Asia. In the present study, we evaluated whether HZ has therapeutic effects on obesity, NAFLD and insulin resistance. The protective effects of HZ extract were examined using free fatty acid-induced steatosis in human HuS-E/2 cells and a high-fat diet-induced NAFLD in mice. The major components of the HZ extract are ugonins J and K, confirmed by HPLC. Incubation of human hepatocytes, HuS-E/2 cells, with palmitate markedly increased lipid accumulation and treatment with the HZ extract significantly decreased lipid deposition and facilitated AMPK and ACC activation. After 12 weeks of a high-fat diet with HZ extract treatment, the HFD mice were protected from hyperlipidemia and hyperglycemia. HZ extract prevented body weight gain, adipose tissue expansion and adipocyte hypertrophy in the HFD mice. In addition, fat accumulation was reduced in mice livers. Moreover, the insulin sensitivity-associated index, which evaluates insulin function, was also significantly restored. These results suggest that HZ has a promising pharmacological effect on high-fat diet-induced obesity, hepatic steatosis and insulin resistance, which may have the potential for clinical application.

    更新日期:2019-12-17
  • Effective fraction of Bletilla striata reduces the inflammatory cytokine production induced by water and organic extracts of airborne fine particulate matter (PM2.5) in vitro
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-16
    Yu-Yao Zu; Quan-Fang Liu; Shu-Xin Tian; Li-Xia Jin; Fu-Sheng Jiang; Mei-Ya Li; Bing-Qi Zhu; Zhi-Shan Ding

    Bletilla striata is a traditional Chinese medicine used to treat hemorrhage, scald, gastric ulcer, pulmonary diseases and inflammations. In this study, we investigated bioactivity of the effective fraction of B. striata (EFB) in reducing the inflammatory cytokine production induced by water or organic extracts of PM2.5. PM2.5 extracts were collected and analyzed by chromatographic system and inductively coupled plasma mass spectrometer. Cell viability was measured using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, and cell supernatant was analyzed by flow cytometry, ELISA, and qRT-PCR in cultured mouse macrophage cell line RAW264.7 treated with EFB and PM2.5 extracts. Expressions of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway were measured by Western blot. PM2.5 composition is complex and the toxicity of PM2.5 extracts were not noticeable. The treatment of EFB at a wide dose-range of 0–40 μg/mL did not cause significant change of RAW264.7 cell proliferation. EFB pretreatment decreased the inflammatory cytokines in the macrophage. Further analysis showed that EFB significantly attenuated PM2.5-induced proinflammatory protein expression and downregulated the levels of phosphorylated NF-κBp65, inhibitor of kappa B (IκB)-α, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38. Our study demonstrated the potential effectiveness of B. striata extracts for treating PM2.5-triggered pulmonary inflammation.

    更新日期:2019-12-17
  • Treatment of migraines with Tianshu capsule: a multi-center, double-blind, randomized, placebo-controlled clinical trial
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-16
    Shengyuan Yu; Ye Ran; Wei Xiao; Wenjing Tang; Jianjun Zhao; Wei Chen; Huikui Zhuang; Cun Ouyang; Hai Lin; Dequan Liu; Tongjun Chen; Hui Huang; Baoshen Wang; Yanlei Hao; Zhongrui Yan; Shike Zhao; Yanling Wang; Jinjun Ni; Chaodong Wang; Wentao Ding; Guoqian Li; Jianhua Cao; Shujuan Tian

    Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3β). The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.

    更新日期:2019-12-17
  • Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-16
    Qiao-ling Fei; Xiao-yu Zhang; Rui-juan Qi; Yun-feng Huang; Yi-xin Han; Xi-meng Li; Run-lan Cai; Yuan Gao; Yun Qi

    Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1β at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75–300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.

    更新日期:2019-12-17
  • The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-12
    Carl Ammoury; Maria Younes; Marianne El Khoury; Mohammad H. Hodroj; Tony Haykal; Peter Nasr; Marilyne Sily; Robin I. Taleb; Rita Sarkis; Rana Khalife; Sandra Rizk

    The edible fruit Annona cherimola has previously shown many nutritional and medicinal properties. The current study evaluates the anti-cancer and anti-proliferative properties of Annona cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines cultured in vitro (Monomac-1 and KG-1). The anti-proliferative effect of A. cherimola ethanolic leaf extract was evaluated via cell viability assay. Its pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining. To further investigate the molecular mechanism by which the extract promoted apoptosis and inhibited the proliferation of the AML cells used, apoptotic protein expression was determined through western blots. Extract composition was elucidated by Gas Chromatography-Mass Spectrometry (GC-MS). Our results showed that the treatment with A. cherimola ethanolic leaf extract exhibited an inhibitory effect on the proliferation of both cancer cell lines used in a dose- and time-dependent manner, with no toxic effects on normal mononuclear cells (MNCs) isolated from human bone marrow. This effect was mediated by DNA fragmentation and apoptosis, as revealed by Cell Death ELISA and dual Annexin V/PI staining. Western blot analysis revealed a Bax/Bcl2 dependent mechanism of apoptosis, as well as PARP cleavage, confirming the apoptotic results observed previously. These effects may be attributed to the presence of terpenes which constitute a large component of the leafy extract, as revealed via GC-MS. All the data presented in our study show that the terpene-rich A. cherimola ethanolic leaf extract exhibits an anti-proliferative and pro-apoptotic effect on the AML cell lines used.

    更新日期:2019-12-13
  • Oral and injectable Marsdenia tenacissima extract (MTE) as adjuvant therapy to chemotherapy for gastric cancer: a systematic review
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-12
    Xu Zhou; Meilu Liu; Qing Ren; Weifeng Zhu; Yang Wang; Haochen Chen; Jianrong Chen

    Marsdenia tenacissima extract (MTE) is a phytochemical widely used as complementary therapy in cancer care. This systematic review was conducted to investigate the anticancer and detoxification effects of MTE, as an adjuvant therapy to chemotherapy, for treating gastric cancer. Ten databases were searched to identify randomized controlled trials (RCTs) comparing oral or injectable MTE plus chemotherapy versus chemotherapy alone for treating gastric cancer up to May 1, 2019. In meta-analyses, proportional odds ratios (PORs) with 95% confidence intervals (CIs) were pooled for the ordinal outcomes using the generalized linear model, and risk ratios (RRs) with 95% CIs were pooled for dichotomous outcomes using the Mantel-Haenszel method. Seventeen RCTs with 1329 individuals were included, with a moderate to high risk of selection and performance bias. Compared to chemotherapy alone, MTE adjuvant therapy significantly improved the response to anticancer treatment (POR 2.01, 95% CI 1.60–2.53) and patients’ performance status (POR 3.15, 95% CI 2.22–4.48) and reduce the incidences of chemotherapy-induced leukopenia (RR 0.66, 95% CI 0.56–0.78), thrombocytopenia (RR 0.64, 95% CI 0.48–0.86), anemia (RR 0.89, 95% CI 0.72–1.10), nausea/vomiting (RR 0.79, 95% CI 0.69–0.91), hepatic injury (RR 0.77, 95% CI 0.61–0.96), and peripheral neurotoxicity (RR 0.77, 95% CI 0.59–1.01). However, MTE did not significantly alleviate anemia, diarrhea, constipation, kidney injury, and oral mucosal lesions after chemotherapy. Incidence of nausea/vomiting was lower in patients receiving oral MTE than those receiving injectable MTE (RR 0.47 vs. 0.82, interaction P = 0.04). Heterogeneity was generally low among these outcomes. Three out of five RCTs that reported survival data supported the effects of MTE for prolonging progression-free and/or overall survival. No studies reported safety outcomes of MTE. The current evidence with limitations of risk of selection and performance bias suggests that MTE, as an adjuvant therapy to chemotherapy, is effective for inhibiting cancer growth and reducing incidences of multiple chemotherapy side effects. Oral MTE may be a better choice. Uncertainty remains regarding the effects of MTE on survival endpoints and the subgroup differences between acute and chronic use of MTE and between different chemotherapy regimens.

    更新日期:2019-12-13
  • A 13-Week Repeated Oral Dose Toxicity Study of ChondroT in Sprague-Dawley Rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-12
    Jiwon Jeong; Kiljoon Bae; Jihoon Kim; Chanhun Choi; Changsu Na; Myeongkyu Park; Youngran Kim; Chang-Seob Seo; Seon-Jong Kim

    ChondroT, a new herbal medication, consists of Angelica grosseserrata Maxim., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis terniflora var. manshurica (Rupr.) Ohwi, and Phellodendron amurense Rupr. (6:4:4:4:3). Our previous studies have shown that ChondroT exhibits significant anti-arthritic and anti-inflammatory effects. In this study, we aimed to assess the toxicological safety assessment of ChondroT. This study was designed to assess the safety of ChondroT after repeated oral administration. Male and female Sprague-Dawley rats were treated with ChondroT at oral doses of 0, 500, 1000, and 2000 mg/kg for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmological findings, urinalysis, hematological and blood-chemical parameters, necropsy findings, organ weights, and histological markers were recorded throughout the study period. Rats were also monitored for an additional 4 weeks to determine the recovery time. No death occurred and no significant changes in food consumption, ophthalmologic findings, and urinalysis were found. Although there were alterations in clinical signs, body weights, hematological parameters, blood-chemical parameters, necropsy findings, organ weights, and histological markers, they were not considered to be toxicologically significant. The results suggest that the no-observed adverse effects level (NOAEL) was 2000 mg/kg/day for the test substance. ChondroT, a new complex herbal medication composed of five plants, can therefore be used safely at the NOAEL.

    更新日期:2019-12-13
  • Lingguizhugan decoction attenuates doxorubicin-induced heart failure in rats by improving TT-SR microstructural remodeling
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-11
    Xueping Li; Guangmin Xu; Shujun Wei; Baocheng Zhang; Huan Yao; Yuchi Chen; Weiwei Liu; Baojia Wang; Juan Zhao; Yongxiang Gao

    Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.

    更新日期:2019-12-11
  • In vitro anti-allergic activity of Moringa oleifera Lam. extracts and their isolated compounds
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-11
    Nur Zahirah Abd Rani; Endang Kumolosasi; Malina Jasamai; Jamia Azdina Jamal; Kok Wai Lam; Khairana Husain

    Moringa oleifera Lam. is a commonly used plant in herbal medicine and has various reported bioactivities such as antioxidant, antimicrobial, anticancer and antidiabetes. It is rich in nutrients and polyphenols. The plant also has been traditionally used for alleviating allergic conditions. This study was aimed to examine the anti-allergic activity of M. oleifera extracts and its isolated compounds. M. oleifera leaves, seeds and pods were extracted with 80% of ethanol. Individual compounds were isolated using a column chromatographic technique and elucidated based on the nuclear magnetic resonance (NMR) and electrospray ionisation mass spectrometry (ESIMS) spectral data. The anti-allergic activity of the extracts, isolated compounds and ketotifen fumarate as a positive control was evaluated using rat basophilic leukaemia (RBL-2H3) cells for early and late phases of allergic reactions. The early phase was determined based on the inhibition of beta-hexosaminidase and histamine release; while the late phase was based on the inhibition of interleukin (IL-4) and tumour necrosis factor (TNF-α) release. Two new compounds; ethyl-(E)–undec-6-enoate (1) and 3,5,6-trihydroxy-2-(2,3,4,5,6-pentahydroxyphenyl)-4H-chromen-4-one (2) together with six known compounds; quercetin (3), kaempferol (4), β-sitosterol-3-O-glucoside (5), oleic acid (6), glucomoringin (7), 2,3,4-trihydroxybenzaldehyde (8) and stigmasterol (9) were isolated from M. oleifera extracts. All extracts and the isolated compounds inhibited mast cell degranulation by inhibiting beta-hexosaminidase and histamine release, as well as the release of IL-4 and TNF-α at varying levels compared with ketotifen fumarate. The study suggested that M. oleifera and its isolated compounds potentially have an anti-allergic activity by inhibiting both early and late phases of allergic reactions.

    更新日期:2019-12-11
  • The effectiveness of traditional Japanese medicine Goshajinkigan in irradiation-induced aspermatogenesis in mice
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-11
    Kumpei Takahashi; Kenta Nagahori; Ning Qu; Miyuki Kuramasu; Yoshie Hirayanagi; Shogo Hayashi; Yuki Ogawa; Naoyuki Hatayama; Hayato Terayama; Kaori Suyama; Shuichi Hirai; Kou Sakabe; Masahiro Itoh

    Infertility and gonadal dysfunction are well known side-effects by cancer treatment in males. In particularly, chemotherapy and radiotherapy induced testicular damage, resulting in prolonged azoospermia. However, information regarding therapeutics to treat spermatogenesis disturbance after cancer treatment is scarce. Recently, we demonstrated that Goshajinkigan, a traditional Japanese medicine, can completely rescue severe busulfan-induced aspermatogenesis in mice. In this study, we aimed to detect the effects of Goshajinkigan on aspermatogenesis after irradiation. This is animal research about the effects of traditional Japanese medicine on infertility after cancer treatment. C57BL/6 J male mice received total body irradiation (TBI: a single dose of 6Gy) at 4 weeks of age and after 60 days were reared a Goshajinkigan (TJ107)-containing or TJ107-free control diet from day 60 to day 120. Then, two untreated females were mated with a single male from each experimental group. On day 60, 120 and 150, respectively, the sets of testes and epididymis of the mice in each group after deep anesthetization were removed for histological and cytological examinations. Histological and histopathological data showed that 6Gy TBI treatment decreased the fertility rate (4/10) in the control diet group; in contrast, in the TJ107-diet group, the fertility rate was 10/10 (p < 0.05 vs. 6Gy group). Supplementation with TJ107 was found to rescue the disrupted inter-Sertoli tight junctions via the normalization of claudin11, occludin, and ZO-1 expression and reduce serum anti-germ cell autoantibodies. These findings show the therapeutic effect on TBI-induced aspermatogenesis and the recovering disrupted gonadal functions by supplementation with TJ107.

    更新日期:2019-12-11
  • Efficacy and safety of oral Guanxinshutong capsules in patients with stable angina pectoris in China: a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-11
    Yang Li; Lei Zhang; Shuzheng Lv; Xiaozeng Wang; Jian Zhang; Xiaoxiang Tian; Yan Zhang; Bojun Chen; Dayue Liu; Jie Yang; Peikang Dong; Yunzhong Xu; Yingmin Song; Junling Shi; Lian Li; Xuechang Wang; Yaling Han

    To assess the efficacy and safety of oral Guanxinshutong (GXST) capsules in Chinese patients with stable angina pectoris (SAP) in a prospective, multicenter, double-Blind, placebo-controlled, randomized clinical trial (clinicaltrials.gov Identifier: NCT02280850). Eligible patients were randomized 1:1 to the GXST or placebo group. Current standard antianginal treatment except for nitrate drugs was continued in both groups, who received an additional 4-week treatment of GXST capsule or placebo. Primary endpoint was the change from baseline in angina attack frequency after the 4-week treatment. Secondary endpoints included the reduction of nitroglycerin dose, score of Seatntle Agina Questionnaire, exercise tolerance test defined as time to onset of chest pain and ST-segment depression at least 1 mm greater than the resting one. A total of 300 SAP patients from 12 centers in China were enrolled between January 2013 and October 2015, and they were randomly divided into the GXST group and the placebo group (150 patients in each group). Of whom, 287 patients completed the study (143 patients in the GXST group, 144 patients in the placebo group). The baseline characteristics of the two groups were comparable. After 4-week treatment with GXST capsules, the number of angina attacks and the consumption of short-acting nitrates were significantly reduced. In addition, the quality of life of patients were also substantially improved in the GXST group. No significant differences in the time of onset of angina and 1-mm ST segment depression were noted between the two groups. 7 patients (4.1%) in the GXST group and 3 patients (2.1%) in the placebo group reported at least one adverse event, respectively. GXST capsules are beneficial for the treatment of SAP patients.

    更新日期:2019-12-11
  • Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-11
    Woo Nam; Seok Hyun Nam; Sung Phil Kim; Carol Levin; Mendel Friedman

    The body responds to overnutrition by converting stem cells to adipocytes. In vitro and in vivo studies have shown polyphenols and other natural compounds to be anti-adipogenic, presumably due in part to their antioxidant properties. Purpurin is a highly antioxidative anthraquinone and previous studies on anthraquinones have reported numerous biological activities in cells and animals. Anthraquinones have also been used to stimulate osteoblast differentiation, an inversely-related process to that of adipocyte differentiation. We propose that due to its high antioxidative properties, purpurin administration might attenuate adipogenesis in cells and in mice. Our study will test the effect purpurin has on adipogenesis using both in vitro and in vivo models. The in vitro model consists of tracking with various biomarkers, the differentiation of pre-adipocyte to adipocytes in cell culture. The compound will then be tested in mice fed a high-fat diet. Murine 3T3-L1 preadipocyte cells were stimulated to differentiate in the presence or absence of purpurin. The following cellular parameters were measured: intracellular reactive oxygen species (ROS), membrane potential of the mitochondria, ATP production, activation of AMPK (adenosine 5′-monophosphate-activated protein kinase), insulin-induced lipid accumulation, triglyceride accumulation, and expression of PPARγ (peroxisome proliferator activated receptor-γ) and C/EBPα (CCAAT enhancer binding protein α). In vivo, mice were fed high fat diets supplemented with various levels of purpurin. Data collected from the animals included anthropometric data, glucose tolerance test results, and postmortem plasma glucose, lipid levels, and organ examinations. The administration of purpurin at 50 and 100 μM in 3T3-L1 cells, and at 40 and 80 mg/kg in mice proved to be a sensitive range: the lower concentrations affected several measured parameters, whereas at the higher doses purpurin consistently mitigated biomarkers associated with adipogenesis, and weight gain in mice. Purpurin appears to be an effective antiadipogenic compound. The anthraquinone purpurin has potent in vitro anti-adipogenic effects in cells and in vivo anti-obesity effects in mice consuming a high-fat diet. Differentiation of 3T3-L1 cells was dose-dependently inhibited by purpurin, apparently by AMPK activation. Mice on a high-fat diet experienced a dose-dependent reduction in induced weight gain of up to 55%.

    更新日期:2019-12-11
  • The combination of Radix Astragali and Radix Angelicae Sinensis attenuates the IFN-γ-induced immune destruction of hematopoiesis in bone marrow cells
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-09
    Juan Liu; Jie Wei; Changzhi Wang; Xiaoying Meng; Hening Chen; Peiying Deng; Meiyier Huandike; Huijie Zhang; Xue Li; Limin Chai

    Radix Astragali and Radix Angelicae Sinensis are two herbs that compose Danggui Buxue Tang (an herbal formula for treatment of anemia diseases). In this study, we explored the molecular mechanism and effective targets to immune destruction of bone marrow (BM) cells treated with Radix Astragali, Radix Angelicae Sinensis or a combination of two agents. The potential synergic advantages of two herbs should also be explored. The constituents of Radix Astragali and Radix Angelicae Sinensis were analyzed by high performance liquid chromatography-electrospray ionization/mass spectrometer system BM cells were separated from limbs of BALB/c mice, and immune destruction was induced with IFN-γ. The percentages of hematopoietic stem cells (HSCs) and CD3+ T cells were detected by flow cytometry. The distribution of T-bet and changes in the combination of SAP and SLAM in BM cells were observed by immunofluorescence. Western blotting was used to assay the expression of key molecules of the eIF2 signaling pathway in BM cells. Seven constituents of Radix Astragali and six constituents of Radix Angelicae Sinensis were identified. The percentages of HSCs increased significantly after treatment with Radix Angelicae Sinensis, especially at high concentrations. The percentages of CD3+ T cells were significantly decreased after Radix Astragali and Radix Angelicae Sinensis treatment. However, the synergistic function of two-herb combinations was superior to that of the individual herbs alone. The distribution of T-bet in BM cells was decreased significantly after Radix Angelicae Sinensis treatment. The number of SLAM/SAP double-stained cells was increased significantly after Radix Astragali treatment at low concentrations. The phosphorylation levels of eIF2α were also reduced after Radix Astragali and Radix Angelicae Sinensis treatment. Radix Astragali and Radix Angelicae Sinensis could intervene in the immunologic balance of T lymphocytes, inhibit the apoptosis of BM cells induced by immune attack, restore the balance of the T cell immune response network and recover the hematopoietic function of HSCs. The synergistic effects of Radix Astragali and Radix Angelicae Sinensis were superior to those of each herb alone.

    更新日期:2019-12-11
  • Clinical evidence-guided network pharmacology analysis reveals a critical contribution of β1-adrenoreceptor upregulation to bradycardia alleviation by Shenxian-Shengmai
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-10
    Jiaming Gao; Taiyi Wang; Xi Yao; Weiwei Xie; Xianru Shi; Shuang He; Tao Zhao; Chunhua Wang; Yan Zhu

    Shenxian-Shengmai (SXSM) Oral Liquid is a CFDA-approved patent Chinese Herbal medicine, which has been clinically used for the treatment of bradycardia. However, its active components and action mechanism remain to be established. The present study aimed to evaluate the efficacy of SXSM on bradycardia and to identify the possible active components and their pharmacological targets for this action. A literature-based meta-analysis was performed to evaluate the clinical efficacy of SXSM on bradycardia, which was confirmed by a rat ex vivo cardiac model. Network pharmacology analysis was then conducted to reveal the potential targets of SXSM active components and their anti-arrhythmia mechanisms. Finally, the identified drug-target interaction was confirmed by immunofluorescence assay in cardiomyocyte. Meta-analysis of the available clinical study data shows that Shenxian-Shengmai Oral Liquid has a favorable effect for bradycardia. In an ex vivo bradycardia model of rat heart, SXSM restored heart rate by affecting Heart rate variability (HRV) which is associated with autonomic nervous system activity. A drug-target-pathway network analysis connecting SXSM components with arrhythmia suggested that a prominent anti-arrhythmia mechanisms of SXSM was via β1-adrenergic signaling pathway, which was subsequently validated by immunofluorescence assay showing that SXSM indeed increased the expression of ADRB1 in cultured cardiomyocytes. By combining approaches of clinical evidence mining, experimental model confirmation, network pharmacology analyses and molecular mechanistic validation, we show that SXSM is an effective treatment for bradycardia and it involves multiple component interacting via multiple pathways, among which is the critical β1-adrenergic receptor upregulation. Our integrative approach could be applied to other multi-component traditional Chinese medicine investigation where ample clinical data are accumulated but advanced mechanistic studies are lacking.

    更新日期:2019-12-11
  • Oolong tea consumption and its interactions with a novel composite index on esophageal squamous cell carcinoma
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-10
    Shuang Liu; Zheng Lin; Liping Huang; Huilin Chen; Yanfang Liu; Fei He; Xiane Peng; Weilin Chen; Ruigang Huang; Wanting Lu; Huimin Yang; Zhisheng Xiang; Zhihui Zhang; Zhijian Hu

    No previous study has investigated the association between oolong tea consumption and esophageal squamous cell carcinoma (ESCC), we aim to elucidate the association between oolong tea consumption and ESCC and its joint effects with a novel composite index. In a hospital-based case-control study, 646 cases of ESCC patients and 646 sex and age matched controls were recruited. A composite index was calculated to evaluate the role of demographic characteristics and life exposure factors in ESCC. Unconditional logistic regression was used to calculate the point estimates between oolong tea consumption and risk of ESCC. No statistically significant association was found between oolong tea consumption and ESCC (OR = 1.39, 95% CI: 0.94–2.05). However, drinking hot oolong tea associated with increased risk of ESCC (OR = 1.60, 95% Cl: 1.06–2.41). Furthermore, drinking hot oolong tea increased ESCC risk in the high-risk group (composite index> 0.55) (OR = 3.14, 95% CI: 1.93–5.11), but not in the low-risk group (composite index≤0.55) (OR = 1.16, 95% CI: 0.74–1.83). Drinking warm oolong tea did not influence the risk of ESCC. No association between oolong tea consumption and risk of ESCC were found, however, drinking hot oolong tea significantly increased the risk of ESCC, especially in high-risk populations.

    更新日期:2019-12-11
  • Alkaloid extract of Corydalis yanhusuo inhibits angiogenesis via targeting vascular endothelial growth factor receptor signaling
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-10
    Li Wan; Yang Zhao; Qun Zhang; Guangyi Gao; Shanlan Zhang; Yong Gao; Xiaofei Chen; Xiaoping Qian

    Corydalis yanhusuo W.T. Wang (YHS) is a well-known Chinese flowering herbal plant commonly used for centuries in functional food and traditional Chinese medicine. In the present study, we have identified and characterized a novel inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) with low toxicity, alkaloid extract of YHS, which suppressed angiogenesis that plays a fundamental role in a wide spectrum of physiological functions and pathological processes. Proliferative ability of human umbilical vascular endothelial cells (HUVECs) was assessed using MTT assay and Ki67 immunofluorescence staining. Migration ability of HUVECs was evaluated by wound healing and transwell assays. In vitro angiogenesis was tested by spheroid sprouting and tube formation assays. In vivo vascularization was examined using Matrigel plug and chick chorioallantoic membrane (CAM) models. Protein expression and phosphorylation levels of VEGFR2, AKT, ERK and STAT3 were determined by Western blot assay. We demonstrated that alkaloid extract of YHS significantly inhibited a variety of VEGF-induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of HUVECs. Moreover, alkaloid extract of YHS contributed to reduced in vivo neo-vessel formation in Matrigel plugs of mice and CAM models. Further mechanistic studies revealed that alkaloid extract of YHS suppressed VEGF-induced signaling pathway as evaluated by diminished phosphorylation of VEGFR2 and subsequently attenuated its downstream regulators including phospho-ERK1/2, phospho-AKT and phospho-STAT3 levels in HUVECs. Collectively, these preclinical findings indicate that alkaloid extract of YHS remarkably limits angiogenesis and may serve as a promising anti-angiogenic drug candidate.

    更新日期:2019-12-11
  • Ethno-pharmacological survey of herbal remedies used in the treatment of paediatric diseases in Buhunga parish, Rukungiri District, Uganda
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-05
    Patience Tugume; Clement Nyakoojo

    Plants have been used as a primary source of medicine since ancient times and about 80% of the world’s population use herbal medicine to treat different ailments. Plant use knowledge differs in space and time and thus requires documentation to avoid its loss from one generation to another. In order to accomplish the survey, semi-structured questionnaires were used. The data collected included names of plant species, parts used, ailments treated, growth habit, methods of preparation and mode of administration of the herbal remedies. Descriptive statistics were used to present the data in form of tables and a graph. Results showed that 50 plant species belonging to 26 families were utilized in the treatment of paediatric diseases of which Asteraceae and Lamiaceae were the most common. Leaves (80%) were the most commonly used and decoctions were the main method of preparation. Twenty nine health conditions were treated out of which digestive disorders, malaria and respiratory tract infections were predominant. Herbs and shrubs were equally dominant. Herbal remedies are an important source of treatment for paediatric diseases in Buhunga Parish. However, there is need for collaboration between herbal medicine users and scientific institutions to help in the discovery of new drugs based on indigenous knowledge. Scientists ought to explore suitable methods of preparation and dosage formulations in order to achieve the best benefits from herbal remedies.

    更新日期:2019-12-06
  • Effects of fish oil supplement on psoriasis: a meta-analysis of randomized controlled trials
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-05
    Shih-Jyun Yang; Ching-Chi Chi

    Fish oils, which contain omega-3 polyunsaturated fatty acids as the active ingredients, possess anti-inflammatory activities and may have therapeutic potential in diseases with an inflammatory etiology. Fish oil supplement has been advocated for treating psoriasis which is a chronic inflammatory dermatosis. We aimed to investigate the effects of fish oil supplement on psoriasis. We searched CENTRAL, Embase and MEDLINE on 24 January 2018 for randomized control trials (RCTs) on the effects of fish oil supplement in treating psoriasis. The Cochrane Collaboration’s tool was used to assess the risk of bias of included RCTs. We performed a random-effects model meta-analysis to obtain the pooled treatment effect estimates. We included 13 RCTs with 625 participants. Three RCTs involving 337 participants provided usable data for meta-analysis. Fish oil supplement did not significantly reduce the severity of psoriasis when assessed by Psoriasis Area and Severity Index score (mean difference − 0.28; 95% confidence interval − 1.74 to 1.19). The current evidence does not support the use of fish oil supplement in treating psoriasis.

    更新日期:2019-12-06
  • Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum leaves and its effect on lung pathological changes in an ovalbumin-induced rat model of asthma
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-04
    Naima Eftekhar; Ali Moghimi; Nema Mohammadian Roshan; Saeideh Saadat; Mohammad Hossein Boskabady

    Ocimum species (Lamiaceae) has been traditionally used for treatment of upper respiratory tract infections, bronchitis, coughs, sore throat, and wound healing. The Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum (O. basilicum) leaves was examined in ovalbumin sensitized animals. Wistar rats were divided to six groups; non-sensitized, sensitized to ovalbumin, sensitized and treated with dexamethasone (1.25 μg/mL), and O. basilicum extract (0.75, 1.50 and 3.00 mg/mL) in drinking water for 21 days. The levels of interleukin 4 (IL-4), interferon gamma (IFN-γ), IFN-γ/IL-4 ratio, immunoglobulin E (IgE), phospholipase A2 (PLA2) and total protein (TP) in BALF, and lung pathological changes were examined. A significant increase in IL-4, IgE, PLA2 and TP levels, all lung pathological indices as well as significant decrease in IFN-γ/IL-4 ratio was seen in the asthmatic compared to the control rats (P < 0.05 to P < 0.001). Treatment with O. basilicum extract resulted in decreased IL-4, IgE, PLA2 and TP levels, but increased IFN-γ/IL-4 ratio compared to untreated sensitized rats (P < 0.01 to P < 0.001). The plant significantly improved the pathological changes of sensitized rats (P < 0.05 to P < 0.01). The improvement effects of higher concentrations of the O. basilicum extract were significantly more than those of dexamethasone (P < 0.05 to P < 0.001). The improvement effects of O. basilicum on pathological changes, immunological and inflammatory markers in sensitized rats comparable or even more potent than dexamethasone suggests the therapeutic potential of the plant in asthma.

    更新日期:2019-12-05
  • ACE inhibitory peptides in standard and fermented deer velvet: an in silico and in vitro investigation
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-05
    Stephen R. Haines; Mark J. McCann; Anita J. Grosvenor; Ancy Thomas; Alasdair Noble; Stefan Clerens

    The use of deer velvet antler (DVA) as a potent traditional medicine ingredient goes back for over 2000 years in Asia. Increasingly, though, DVA is being included as a high protein functional food ingredient in convenient, ready to consume products in Korea and China. As such, it is a potential source of endogenous bioactive peptides and of ‘cryptides’, i.e. bioactive peptides enzymatically released by endogenous proteases, by processing and/or by gastrointestinal digestion. Fermentation is an example of a processing step known to release bioactive peptides from food proteins. In this study, we aimed to identify in silico bioactive peptides and cryptides in DVA, before and after fermentation, and subsequently to validate the major predicted bioactivity by in vitro analysis. Peptides that were either free or located within proteins were identified in the DVA samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by database searching. Bioactive peptides and cryptides were identified in silico by sequence matching against a database of known bioactive peptides. Angiotensin-converting enzyme (ACE) inhibitory activity was measured by a colorimetric method. Three free bioactive peptides (LVVYPW, LVVYPWTQ and VVYPWTQ) were solely found in fermented DVA, the latter two of which are known ACE inhibitors. However matches to multiple ACE inhibitor cryptides were obtained within protein and peptide sequences of both unfermented and fermented DVA. In vitro analysis showed that the ACE inhibitory activity of DVA was more pronounced in the fermented sample, but both unfermented and fermented DVA had similar activity following release of cryptides by simulated gastrointestinal digestion. DVA contains multiple ACE inhibitory peptide sequences that may be released by fermentation or following oral consumption, and which may provide a health benefit through positive effects on the cardiovascular system. The study illustrates the power of in silico combined with in vitro methods for analysis of the effects of processing on bioactive peptides in complex functional ingredients like DVA.

    更新日期:2019-12-05
  • Anti-HIV-1 protease activity of the crude extracts and isolated compounds from Auricularia polytricha
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-05
    Chanin Sillapachaiyaporn; Sunita Nilkhet; Alison T. Ung; Siriporn Chuchawankul

    Acquired immunodeficiency syndrome (AIDS) is caused by the Human immunodeficiency virus type-1 (HIV-1). HIV-1 protease (HIV-1 PR) is an essential enzyme for the HIV replication, and therefore, it is an important target for antiretroviral drugs development, particularly from natural products. Auricularia polytricha (AP) is an edible mushroom with several important therapeutic properties. These properties will be investigated as HIV-1 PR inhibitors. The sequential hexane (APH), ethanol (APE) and water (APW) extracts from AP were screened for inhibitory activity against HIV-1 PR. The extract that consistently showed the strong HIV-1 PR inhibition was further investigated for its phytochemical constituents. The compounds were purified by column chromatography. The isolated compounds were structurally elucidated using 1D and 2D NMR, HRMS, FTIR, and GC/MS techniques. Each compound was screened against HIV-1 PR to determine its inhibitory activity and to provide an explanation for the activity found in the extract. Hexane crude extract of AP (APH) exhibited significant inhibition on HIV-1 PR activity. Four major compounds isolated from APH fraction were identified to be two triacylglycerols, linoleic acid and ergosterol. Moreover, all four compounds showed significant inhibition of HIV-1 PR activity. The findings from this study suggest that AP is a good source of fatty esters, fatty acids and ergosterol. These natural products exhibit anti-HIV-1 properties by blocking HIV-1 PR. These important biological results warrant further development of AP as an alternative antiretroviral drug.

    更新日期:2019-12-05
  • Systems pharmacology based approach to investigate the in-vivo therapeutic efficacy of Albizia lebbeck (L.) in experimental model of Parkinson’s disease
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-05
    Uzma Saleem; Zohaib Raza; Fareeha Anwar; Zunera Chaudary; Bashir Ahmad

    Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra pars compacta and clinically manifested mainly with motor dysfunctions. Plants are rich source of medicinally important bioactive compounds and inhabitants of underdeveloped countries used plants for treatment of various ailments. Albizia lebbeck has been reported to possess antioxidant and neuroprotective properties that suggest the evaluation of its traditional therapeutic potential in neurodegenerative diseases. The aim of present study was to validate the traditional use of Albizia lebbeck (L.) and delineate its mechanism of action in PD. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD. The haloperidol-induced catalepsy was adopted as experimental model of PD for in-vivo studies in wistar albino rats. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD. In-vivo studies revealed that Albizia lebbeck improved the motor functions and endurance as demonstrated in behavioral studies which were further supported by the rescue of endogenous antioxidant defense and reversal of ultrastructural damages in histological studies. System pharmacology approach identified 25 drug like compounds interacting with 132 targets in a bipartite graph that revealed the synergistic mechanism of action at system level. Kaemferol, phytosterol and okanin were found to be the important compounds nodes with prominent target nodes of TDP1 and MAPT. The therapeutic efficiency of Albizia lebbeck in PD was effectively delineated in our experimental and systems pharmacology approach. Moreover, this approach further facilitates the drug discovery from Albizia lebbeck for PD.

    更新日期:2019-12-05
  • Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-05
    Yuyan Fan; Hongyu Fan; Bin Zhu; Yilun Zhou; Qingshan Liu; Ping Li

    Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS). DN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro. Treatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment. These novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.

    更新日期:2019-12-05
  • Experimental validation and computational modeling of anti-influenza effects of quercetin-3-O-α-L-rhamnopyranoside from indigenous south African medicinal plant Rapanea melanophloeos
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-02
    Parvaneh Mehrbod; Samad Nejad Ebrahimi; Fatemeh Fotouhi; Fatemeh Eskandari; Jacobus N. Eloff; Lyndy J. McGaw; Folorunso O. Fasina

    Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking. MDCK cells were exposed to Q3R and 100CCID50/100 μl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R. The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of − 10.81, − 10.47, − 9.52, − 9.24 and − 8.78 Kcal/mol, respectively. Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.

    更新日期:2019-12-03
  • Anti-inflammatory effects of a methanol extract of Dictamnus dasycarpus Turcz. root bark on imiquimod-induced psoriasis
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-02
    Minjee Choi; Jun Koo Yi; Si-Yong Kim; Jung Hyun Ryu; Jinhee Lee; Wookbong Kwon; Soyoung Jang; Dongjun Kim; MyoungOk Kim; Hyungwoo Kim; Sung Hyun Kim; Seong-Kyoon Choi; Zae Young Ryoo

    The root bark of Dictamnus dasycarpus Turcz. has been successfully used for the treatment of inflammatory skin conditions such as eczema and pruritus. However, the anti-psoriatic effect of this plant has not until now been investigated. The aim of this project was to investigate whether a methanol extract of Dictamnus dasycarpus Turcz. root bark (MEDD) can be used as a therapeutic agent for psoriasis in C57BL/6 mice model of imiquimod (IMQ)-induced psoriasis. IMQ and MEDD was applied to mouse skin continuously for 7 days. The skin phenotype and the levels of inflammatory cytokines, such as interferon (IFN)-γ and interleukin (IL)-17, were analyzed. The immune cell population was determined by flow cytometry, and STAT1 and 3 protein levels were measured. An alleviation of scaly skin phenotype, immune cell infiltration in the dermis, and epidermal hyperplasia was observed after daily MEDD treatment in the lesion-affected area. It was also found that MEDD reduced IL-17 cytokine levels decreased by 44.37% (p < 0.05), the number of IL-17-producing Th17 cells and γδT cells, and the size of the Th1 population secreting IFN-γ decreased by 45.98, 62.21, and 44.42%, respectively (p < 0.05), compared with the vehicle control group. STAT3 signals, associated with IL-17 are also reduced by MEDD. An anti-psoriatic effect of MEDD was observed, as determined by decreased skin inflammation, reduced number of inflammatory cytokines, and a smaller population of inflammatory cells. These results contribute to the validation of the use of MEDD in the treatment of psoriasis.

    更新日期:2019-12-03
  • Pharmacological and computational evaluation of fig for therapeutic potential in hyperactive gastrointestinal disorders
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-03
    Muhammad Bilal Riaz; Arif-ullah Khan; Neelam Gul Qazi

    Ficus palmata (Fig), are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including inflammation, tumor, epilepsy, jaundice, influenza and bacillary dysentery. The present study aimed to evaluate the antidiarrheal, antisecretary, antispasmodic, antiulcer and anti motility properties of Ficus palmata. In-vivo, in-vitro and in-silico techniques were used to investigate various gastrointestinal effects of Ficus palmata. Antidiarrheal, antisecretary, antispasmodic, antiulcer, anti motility and molecular docking were performed using castor oil induced diarrhea and fluid accumulation, isolated tissue preparations, ethanol-HCl induced ulcer assay, charcoal meal transit time and Auto Doc Vina. Ficus palmata crude extract (Fp.Cr) exhibited protection against castor oil-induced diarrhea in mice and dose-dependently inhibited intestinal fluid secretions. Fp.Cr caused relaxation of spontaneous and K+ (80 Mm)-induced contractions in isolated rabbit jejunum preparations. It showed protective effect against gastric ulcers induced by ethanol-hydrochloric acid in rats. Fp.Cr reduced distance travelled by charcoal meal in the gastrointestinal transit model in mice. The plant constituents: psoralenoside and bergapten showed high binding affinities (E-value ≥ − 6.5 Kcal/mol) against histaminergic H1, calmodulin and voltage gated L-type calcium channels, while showed moderate affinities (E-value ≥7 Kcal/mol) against dopaminergic D2, adrenergic α1, muscranic M3, mu-opioid, whereas revealed lower affinities (E-value ≥9.5 Kcal/mol) vs. muscranic M1, histaminergic H2 and H+/K+ ATPase pump. Germanicol acetate and psoralene exhibited weak affinities against aforementioned targets. This study reveals that Ficus palmata possesses anti-diarrheal, anti-secretory, anti-spasmodic, anti-motility and anti-ulcer activities. The various constituents reveal different binding affinities against target proteins, which mediate the gastrointestinal functions.

    更新日期:2019-12-03
  • The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-02
    Kathleen F. Benson; Paul Stamets; Renee Davis; Regan Nally; Alex Taylor; Sonya Slater; Gitte S. Jensen

    The medicinal mushroom Trametes versicolor (Tv, Turkey Tail) is often prepared for consumption as a powder from the fungal mycelium and the fermented substrate on which it grew. The goal for this study was to evaluate the immune-modulating properties of the mycelium versus the fermented substrate, to document whether an important part of the immune-activating effects resides in the metabolically fermented substrate. Tv mycelium was cultured on rice flour. The mycelium and the fermented substrate were mechanically separated, dried, and milled. The initial substrate served as a control. Aqueous fractions were extracted and passed through 0.22-μm filters. The remaining solids were passed through homogenization spin columns without filtration. The aqueous and solid fractions of the initial substrate (IS), the fermented substrate (FS), and the Trametes versicolor mycelium (TvM) were tested for immune-activating and modulating activities on human peripheral blood mononuclear cell cultures, to examine expression of the CD69 activation marker on lymphocytes versus monocytes, and on the T, NKT, and NK lymphocyte subsets. Culture supernatants were tested for cytokines using Luminex arrays. Both aqueous and solid fractions of TvM triggered robust induction of CD69 on lymphocytes and monocytes, whereas FS only triggered minor induction of CD69, and IS had no activating effect. The aqueous extract of TvM had stronger activating effects than the solid fraction. In contrast, the solid fraction of IS triggered a reduction in CD69, below levels on untreated cells. Both aqueous and solid fractions of FS triggered large and dose-dependent increases in immune-activating pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10), anti-viral cytokines interferon-gamma (IFN-γ) and Macrophage Inflammatory Protein-alpha (MIP-1α), as well as Granulocyte-Colony Stimulating Factor (G-CSF) and Interleukin-8 (IL-8). TvM triggered more modest cytokine increases. The aqueous extract of IS showed no effects, whereas the solid fraction showed modest effects on induction of cytokines and growth factors. The results demonstrated that the immune-activating bioactivity of a mycelial-based medicinal mushroom preparation is a combination of the mycelium itself (including insoluble beta-glucans, and also water-soluble components), and the highly bioactive, metabolically fermented substrate, not present in the initial substrate.

    更新日期:2019-12-02
  • Water-separated part of Chloranthus serratus alleviates lipopolysaccharide- induced RAW264.7 cell injury mainly by regulating the MAPK and Nrf2/HO-1 inflammatory pathways
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-02
    Shuping Sun; Yunyan Du; Chuanliu Yin; Xiaoguo Suo; Rui Wang; Rongping Xia; Xiaoping Zhang

    Chloranthus serratus (Chloranthaceae) has been used to treat bruises, rheumatoid and bone pain. However, the anti-inflammatory mechanisms of C. serratus in vitro have not been fully elucidated. The present study aimed to explore the anti-inflammatory activity and potential mechanisms of C. serratus’s separated part of water (CSSPW) in lipopolysaccharide (LPS)-induced RAW264.7 cells. The concentrations of CSSPW were optimized by CCK-8 method. Nitric oxide (NO) content was detected by one-step method. The levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by real-time quantitative PCR (qPCR). Immunofluorescence and DCFH-DA fluorescent probes were used to detect p65 nuclear translocation and reactive oxygen species (ROS) content, respectively. Western blotting was used to assay the protein expression of mitogen-activated protein kinases (MAPK), nuclear factor-kappa B (NF-κB) and nuclear transcription factor E2 related factor 2/haem oxygenase-1 (Nrf2/HO-1) pathways. The final concentrations of 15 ng/mL, 1.5 μg/mL and 150 μg/mL were selected as low, medium and high doses of CSSPW, respectively. CSSPW treatment significantly reduced the generation of NO, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandinE2 (PGE2), iNOS mRNA and COX-2 mRNA in response to LPS stimulation. Furthermore, the protein expression of the MAPK and NF-κB pathways was suppressed by CSSPW treatment, as well as p65 nuclear translocation and ROS production. In contrast, the protein expression of the Nrf2/HO-1 pathway was markedly upregulated. CSSPW exerts its anti-inflammatory effect via downregulating the production of pro-inflammatory mediators, inhibiting the activation of NF-κB and MAPK pathways, as well as activating Nrf2/HO-1 pathway in LPS-induced RAW264.7 cells.

    更新日期:2019-12-02
  • Mangosteen (Garcinia mangostana) flesh supplementation attenuates biochemical and morphological changes in the liver and kidney of high fat diet-induced obese rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-02
    Noratirah Shazlin Muhamad Adyab; Asmah Rahmat; Noor Atiqah Aizan Abdul Kadir; Hawa Jaafar; Radhiah Shukri; Nurul Shazini Ramli

    Mangosteen is a native fruit from Southeast Asia. It is rich in phenolic compounds such as xanthones, anthocyanins and phenolic acids. Mangosteen pericarp extract showed inhibitory activity towards pancreatic lipase and may have potential use for obesity treatment. However, there is limited study on the beneficial effects of mangosteen flesh against obesity. This study aimed to investigate the effects of Garcinia mangostana flesh (GMF) on biochemical and morphological changes in the liver and kidney of high-fat diet-induced obese rats. Forty healthy Sprague-Dawley rats were randomised into five groups (n = 8) with four groups were fed with high-fat diet (HFD) for 10 weeks and a control group was fed with rat chow diet. Supplementation with GMF in obese rats was continued for 7 weeks starting from week 10th after the initiation of HFD at different doses (200 mg/kg, 400 mg/kg and 600 mg/kg). The positive and negative control rats were given distilled water via oral gavage. Plasma lipid profile, antioxidant enzymes and pro-inflammatory markers were determined using commercial kits. Liver and kidney structure were defined by histology. The rats fed with HFD for 10 weeks increased plasma LDL-cholesterol, reduced plasma glutathione peroxidase level and had significantly higher body weight compared to normal control rats (p < 0.05). Obese rats also showed elevated level of TNF-α and IL-6 after 17 weeks of HFD. Supplementation with GMF for 7 weeks in obese rats reduced their body weight, improved lipid profile, increased total antioxidant capacity and glutathione peroxidase level and lowered plasma pro-inflammatory markers (TNF-α and IL-6) (p < 0.05). In addition, GMF supplementation attenuated the abnormalities of the liver and kidney tissue caused by high fat diet. Taken together, the findings suggest that supplementation of Garcinia mangostana flesh may help in reducing body weight and has the potential to ameliorate the biochemical changes of the high fat diet-induced obesity in rats. Further studies on pharmacodynamic and pharmacokinetic are required before the results are translated to human.

    更新日期:2019-12-02
  • Antiulcerogenic effect of Cuphea ignea extract against ethanol-induced gastric ulcer in rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-12-02
    Amria M. Mousa; Nermin M. El-Sammad; Sherien K. Hassan; Abd El Nasser A. Madboli; Amani N. Hashim; Eman S. Moustafa; Sherien M. Bakry; Elsayed A. Elsayed

    Cuphea ignea is one of the herbal resources belonging to Lythraceae family. Some species of this family have been used traditionally in South and Central America’s folk medicine for treating stomach disorders. Therefore, the present study was performed to evaluate the gastropreventive effect of aqueous ethanolic extract of C. ignea aerial parts on ethanol-induced gastric ulcer. Gastric ulcers were induced in Sprague Dawley rats using one oral dose of absolute ethanol (1.5 mL/rat). The C. ignea aerial parts extract at doses of 250 and 500 mg/kg body weight and ranitidine (a reference drug) at a dose of 30 mg/kg body weight were orally administrated daily for 7 days before ulcer induction. One hour after ethanol administration blood samples were collected and then stomachs of sacrificed rats were subjected to biochemical, macroscopic and microscopic studies. Oral administration of C. ignea extract significantly attenuated gastric ulcer as revealed by significant reduction in the gastric ulcer index and volume of gastric juice while significantly increased preventive percentage, gastric pH value and pepsin activity. Pre-treatment of C. ignea extract markedly improved the serum level of TNF-α, the gastric MPO activity and NO content. Furthermore, C. ignea pre-treatment significantly increased the gastric levels of enzymatic and non- enzymatic antioxidants namely CAT, SOD, GSH-Px, and GSH with concomitant reduction in MDA level compared with those in the ethanol group. These results were further supported by histopathological findings which revealed the curing effect of C. ignea on the hemorrhagic shock induced by ethanol toxicity. C. ignea extract showed a potential gastroprotective effect on ethanol-induced gastric ulcer, and its effect may be mediated through suppression of oxidative stress and gastric inflammation.

    更新日期:2019-12-02
  • 1α, 25-dihydroxy Vitamin D3 containing fractions of Catharanthus roseus leaf aqueous extract inhibit preadipocyte differentiation and induce lipolysis in 3T3-L1 cells
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-29
    Anuj Kumar Borah; Archana Singh; Rafika Yasmin; Robin Doley; Venkata Satish Kumar Mattaparthi; Sougata Saha

    To investigate the potential of Catharanthus roseus leaf aqueous crude extract (CRACE) as a regulator of adipocyte development and function. 3T3-L1 adipogenesis model was used to investigate the effect of CRACE on adipogenesis. 3T3-L1 preadipocytes (for adipogenic differentiation) and mature 3T3-L1 adipocytes (for adipocyte function) were treated with non-toxic doses of CRACE. The outcomes were corroborated by intracellular lipid accumulation, expression of pro-and anti-adipogenic effector molecules. To investigate CRACE mediated lipolysis, cAMP accumulation, glycerol release and phosphorylation of key effector molecules were tested in treated mature adipocytes. Finally, the extract was fractionated to identify the active molecule/s in the extract. CRACE significantly reduced adipocyte differentiation by modulating PPARγ expression. At early stage CRACE directly targeted Lipin1 expression and consequently impacted KLF7, subsequently expression of GATA2, CEBPα, SREBP1c were targeted, with PPARγ expression, particularly curtailed. While CRACE significantly reduced several lipogenic genes like FAS and GPD1 in mature adipocytes, concomitantly, it greatly increased lipolysis resulting in decreased lipid accumulation in mature adipocytes. The increase in lipolysis was due to decreased Akt activation, increased cAMP level, and PKA activity. The fractionation of CRACE allowed identification of two fractions with potent anti-adipogenic activity. Both the fractions contained 1α, 25-dihydroxy Vitamin D3 as major component. 1α, 25-dihydroxy Vitamin D3 containing CRACE can be developed into an effective anti-obesity formulation that decreases adipogenesis and increases lipid catabolism.

    更新日期:2019-11-30
  • Ameliorative effects of aqueous extract of Forsythiae suspensa fruits on oxaliplatin-induced neurotoxicity in vitro and in vivo
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-29
    Jin-Mu Yi; Sarah Shin; No Soo Kim; Ok-Sun Bang

    The dried fruits of Forsythia suspensa has generally been used to clear heat and detoxify in traditional Korean and Chinese medicine. Oxaliplatin is a first-line treatment chemotherapeutic agent for advanced colorectal cancer, but it induces peripheral neuropathy as an adverse side effect affecting the treatment regimen and the patient’s quality of life. The present study was conducted to evaluate the neuroprotective effects of an aqueous extract of F. suspensa fruits (EFSF) on oxaliplatin-induced peripheral neuropathy. The chemical components from EFSF were characterized and quantified using the ultra-high performance liquid chromatography-diode array detector system. The cytotoxicities of anticancer drugs in cancer cells and PC12 cells were assessed by the Ez-Cytox viability assay. To measure the in vitro neurotoxicity, the neurite outgrowth was analyzed in the primary dorsal root ganglion (DRG) cells, and neural PC12 cells that were differentiated with nerve growth factor. To evaluate the in vivo neuroprotective activity, the von Frey test was performed in six-week-old male mice (C57BL/6) receiving EFSF (60–600 mg/kg) in the presence of 20–30 mg/kg cumulative doses of oxaliplatin. Thereafter, the mice were euthanized for immunohistochemical staining analysis with an antibody against PGP9.5. EFSF attenuated the cytotoxic activities of the various anticancer drugs in neural PC12 cells, but did not affect the anticancer activity of oxaliplatin in human cancer cells. Oxaliplatin remarkably induced neurotoxicities including cytotoxicity and the inhibited neurite outgrowth of DRG and neural PC12 cells. However, the co-treatment of EFSF (100 μg/ml) with oxaliplatin completely reversed the oxaliplatin-induced neurotoxicity. Forsythoside A, the major component of EFSF, also exerted remarkable neuroprotective effects against the oxaliplatin-induced neurotoxicity. In addition, EFSF (60–200 mg/kg) significantly alleviated the oxaliplatin-induced mechanical allodynia and loss of intra-epidermal nerve fiber to the levels of the vehicle control in the mouse peripheral neuropathy model. EFSF could be considered a useful herbal medicine for the treatment of peripheral neuropathy in cancer patients receiving chemotherapy with oxaliplatin.

    更新日期:2019-11-30
  • Antitumor and antioxidant effects of Clinacanthus nutans Lindau in 4 T1 tumor-bearing mice
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-29
    Nik Mohd Afizan Nik Abd Rahman; M. Y. Nurliyana; M. N. F. Natasha Nur Afiqah; Mohd Azuraidi Osman; Muhajir Hamid; Mohd Azmi Mohd Lila

    Clinacanthus nutans Lindau (C. nutans) is a species of in Acanthaceae family and primarily used in South East Asian countries. C. nutans is well known as Sabah snake grass in Malaysia, and its leaves have diverse medicinal potential in conventional applications, including cancer treatments. On the basis of literature search, there is less conclusive evidence of the involvement of phytochemical constituents in breast cancer, in particular, animal tumor models. The current study aimed to determine the antitumor and antioxidant activities of C. nutans extract in 4 T1 tumor-bearing mice. C. nutans leaves were subjected to methanol extraction and divided into two different concentrations, 200 mg/kg (low-dose) and 1000 mg/kg (high-dose). The antitumor effects of C. nutans extracts were assessed using bone marrow smearing, clonogenic, and splenocyte immunotype analyses. In addition, hematoxylin and eosin, tumor weight and tumor volume profiles also used to indicate apoptosis appearance. Serum cytokine levels were examined using ELISA assay. In addition, nitric oxide assay reflecting antioxidant activity was performed. From the results obtained, the methanol extract of C. nutans leaves at 200 mg/kg (P < 0.05) and 1000 mg/kg (P < 0.05) showed a significant decrease in nitric oxide (NO) and malondialdehyde (MDA) levels in the blood. On the other hand, C. nutans extract (1000 mg/kg) also showed a significant decrease in the number of mitotic cells, tumor weight, and tumor volume. No inflammatory and adverse reactions related to splenocytes activities were found in all treated groups of mice. Despite its promising results, the concentration of both C. nutans extracts have also reduced the number of colonies formed in the liver and lungs. In conclusion, C. nutans extracts exert antitumor and antioxidant activities against 4 T1 mouse breast model with no adverse effect and inflammatory response at high dose of 1000 mg/kg, indicating an effective and complementary approach for cancer prevention and treatment.

    更新日期:2019-11-30
  • Use of traditional and complementary medicine among Norwegian cancer patients in the seventh survey of the Tromsø study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-29
    Agnete Egilsdatter Kristoffersen; Trine Stub; Ann Ragnhild Broderstad; Anne Helen Hansen

    Traditional and complementary medicine (T&CM) is commonly used by cancer patients in Northern Norway, in particular spiritual forms like traditional healing. T&CM is mainly used complementary to conventional cancer treatment and is rarely discussed with conventional health care providers, increasing the risk of negative interaction with conventional cancer care. The aim of this study was to investigate the use of T&CM among cancer patients in Tromsø, and to investigate the differences in T&CM use between people living with cancer, people with cancer previously, and people without a history of cancer. Data was drawn from the seventh survey of the Tromsø study conducted in 2015–2016. All inhabitants of Tromsø aged 40 and above were invited to participate (n = 32,591) of whom n = 21,083 accepted the invitation (response rate 65%). Data was collected thorough three self-administered questionnaires and a comprehensive clinical examination. Pearson chi-square tests, Fisher exact tests and one-way ANOVA tests were used to describe differences between the groups while binary logistic regressions were used for adjusted values. Eight percent of the participants (n = 1636) reported to have (n = 404) or have had (n = 1232) cancer. Of the participants with cancer at present 33.4% reported use of T&CM within the last year, 13.6% had consulted a T&CM provider, 17.9% had used herbal medicine/natural remedies and 6.4% had practiced self-help techniques. The participants with cancer at present were more likely to have visited a T&CM provider than participants with cancer previously (13.6% vs. 8.7%, p = 0.020). Among the participants with cancer at present, 6.4% reported to have consulted a TM provider, 5.8% had consulted an acupuncturist, while 4.7% had consulted other CM providers. Women were significantly more likely than men to have used acupuncture and self-help techniques. No significant gender differences were found regarding visits to other CM providers, TM providers nor use of herbal medicine/natural remedies. The findings are in line with previous research suggesting that both men and women use TM complementary to other CM modalities outside the official health care system. As herbal medicine might interact with conventional cancer treatment, health care providers need to discuss such use with their patients.

    更新日期:2019-11-30
  • Biological safety of Electroacupuncture with STS316 needles
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-10-28
    Kwang-Ho Choi; Sun Hee Yeon; Seong Jin Cho; O Sang Kwon; Sanghun Lee; Su Yeon Seo; Suk-Yun Kang; Yeonhee Ryu

    Electroacupuncture (EA) is often used in clinical settings due to its analgesic effect, but its safety has not been verified due to the lack of clear criteria. This study examined the critical range of the corrosion of stainless steel types STS304 and STS316, which have been used clinically, and the relationship between needle corrosion and cell necrosis. The critical point of corrosion for STS304 and STS316 was identified by varying the time, frequency, and stimulation intensity. In a tissue necrosis experiment, EA stimulation was applied to rats using STS316 needles with different thicknesses at maximum intensity for 60 min, and the presence of corrosion and tissue necrosis was determined. A cytotoxicity experiment was also conducted and assessed the needles and tissue necrosis. The results showed that STS316 was more stable than STS304 and that only coated needles corroded. Furthermore, tissue necrosis was observed regardless of corrosion, and slight cell necrosis was associated with needles with corrosion. This study demonstrated that non-coated STS316 was the most stable for EA stimulation and that corrosion byproducts and cell necrosis were not directly related.

    更新日期:2019-11-28
  • Remarkable rutin-rich Hypericum capitatum extract exhibits anti-inflammatory effects on turpentine oil-induced inflammation in rats
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-10-29
    Anca D. Farcas; Augustin C. Mot; Cezara Zagrean-Tuza; Madalina Ticolea; Bogdan Sevastre; Muhittin Kulak; Radu Silaghi-Dumitrescu; Alina Parvu

    Natural extracts with beneficial biological activities are nowadays of high interest, in various treatment or prophylaxis. Hypericum capitatum has been known for its curative effects for centuries and its extracts have become of interest due to their distinct activity among other Hypericaceae members. In this study, further light is aimed to be shed on the secondary-metabolites composition of H. capitatum extracts, using chromatographic techniques and Electron paramagnetic resonance profiles in alkaline medium. Considering that no previous works explored the anti-inflammatory activity of H. capitatum, here, an in vivo study is also designed in order to evaluate this property by assessing the impact of one of H. capitatum extracts in ameliorating turpentine oil-induced inflammation on rats and to quantify their blood antioxidants level. Chromatographic techniques and Electron paramagnetic resonance spectroscopy were used in order to describe the chemical profile in different parts of the plant. The in vivo study on turpentine-oil induced inflammation in rats included three doses of H. capitatum extract expressed in rutin concentration. Oxidative stress was measured using total oxidative status, total antioxidant capacity, oxidative stress index, 3-nitrotyrosine, nitric oxide, malondialdehyde, superoxide dismutase, catalase and the inflammatory response was evaluated by performing a complete blood cells count and C reactive protein. The extract was remarkably rich in rutin; however, other polyphenolic-like minor components appeared important in explaining the observed biological properties. The tested extract prevents the increase of inflammation-induced white blood cell count, number of neutrophils, and serum nitric oxide, and did so in a dose-dependent manner, similarly to the positive control—diclofenac. In addition, the same extract appeared to be a good alternative to diclofenac to restore total oxidative status, thiobarbituric active reactive species, total proteins and C reactive proteins. Moreover, antioxidant enzymes such as catalase, superoxide dismutase and total serum thiol concentration were significantly increased by the tested extract. Due to its powerful reservoir rich in rutin, H. capitatum extract depicted its in vivo antioxidant and anti-inflammatory effects indicating it to be a good alternative to conventional drugs for oxidative stress protection.

    更新日期:2019-11-28
  • Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-10-30
    Abid Nordin; Haziq Kamal; Muhammad Dain Yazid; Aminuddin Saim; Ruszymah Idrus

    Nigella sativa or commonly known as black seed or black cumin is one of the most ubiquitous complementary medicine. Epithelial to mesenchymal transition (EMT) of type 2 is defined by the balance between wound healing and tissue fibrosis, which is dependent to the state of inflammation. This systematic review is conducted to provide an overview regarding the reported effect of Nigella sativa and its bioactive compound on the type 2 EMT. A search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT. A total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone. Through this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.

    更新日期:2019-11-28
  • Anti-inflammatory effect of Vaccinium oldhamii stems through inhibition of NF-κB and MAPK/ATF2 signaling activation in LPS-stimulated RAW264.7 cells
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-04
    Ha Na Kim; Jueng Kyu Baek; Su Bin Park; Jeong Dong Kim; Ho-Jun Son; Gwang Hun Park; Hyun Ji Eo; Jae Ho Park; Hyuk-Sang Jung; Jin Boo Jeong

    Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of α-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. Cell viability was evaluated by MTT assay. The determination of NO and PGE2 production was performed using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The change of mRNA or protein level was evaluated by RT-PCR and Western blot. Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. These results indicate that VOS may exert anti-inflammatory activity by inhibiting NF-κB and MAPK/ATF2 signaling. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

    更新日期:2019-11-28
  • Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-04
    S. Santos; C. Haslinger; M. Mennet; U. von Mandach; M. Hamburger; A. P. Simões-Wüst

    The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ). Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1–41 cell lines. BPJ (2.5 μg/mL), atosiban (0.27 μg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability. BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.

    更新日期:2019-11-28
  • The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-04
    Sidney J. Stohs; C. Y. O. Chen; Harry G. Preuss; Sidhartha D. Ray; Luke R. Bucci; Jin Ji; Kevin J. Ruff

    Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. Hydrolysis of blood plasma samples prior to extraction and reporting the results as “curcumin” obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. ClinicalTrails.gov, trial identifying number NCT04103788 , September 24, 2019. Retrospectively registered.

    更新日期:2019-11-28
  • The potential of antioxidant-rich Maoberry (Antidesma bunius) extract on fat metabolism in liver tissues of rats fed a high-fat diet
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-04
    Chattraya Ngamlerst; Arunwan Udomkasemsab; Ratchanee Kongkachuichai; Karunee Kwanbunjan; Chaowanee Chupeerach; Pattaneeya Prangthip

    Obesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFLD is the most common liver disease and is rapidly becoming a global public health problem. Maoberry (Antidesma bunius) is a fruit rich in antioxidants, especially phenolic compounds, which are reported to have benefits for patients with NAFLD. We evaluated the effect of Maoberry extract on fat metabolism in liver tissues of high fat diet–induced rats. Five (5) groups (n = 12) of male Sprague-Dawley (SD) rats were divided into those given a high fat diet with no treatment (HF), different dosages of Maoberry extracts (0.38 [ML], 0.76 [MM) and 1.52 [MH] g/kg body weight) and 10 mg/kg statin (STAT). The rats were fed a high fat diet for 4 weeks to induce obesity and subsequently continued more for 12 weeks with treatments of Maoberry extracts or STAT. The levels of triglyceride, liver enzymes, oxidative stress and inflammation markers, triglyceride synthesis regulators, and pathology of the liver in high fat diet-induced rats were investigated. Feeding Maoberry extract in MH groups resulted in decreasing levels of serum alanine aminotransferase (ALT), liver triglyceride, liver thiobarbituric acid reactive substances (TBARS) and mRNA expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, glycerol-3-phosphate acyltransferase (GPAT)-1 and acetyl-coenzyme A carboxylase (ACC) compared with the HF group (P < 0.05). Moreover, histopathological study of the liver showed reduced fat droplets in the Maoberry extract treatment groups, especially in MH groups and STAT treatment groups. The improvements of fat metabolism in liver tissues of rats fed a high-fat diet were observed in Maoberry extracts treatment groups. The underline mechanism that link to fat metabolism might be through the process accompanied with down-regulated the gene expression of key enzymes of lipid production, antioxidant activity, and anti-inflammation properties of Maoberry extracts which contains high levels of phenolic and flavonoid compounds.

    更新日期:2019-11-28
  • Identification and characterization of the Cucurbitacins, a novel class of small-molecule inhibitors of Tropomyosin receptor kinase a
    BMC Complement. Altern. Med. (IF 2.479) Pub Date : 2019-11-06
    Yueling Zhong; Hong Xu; Yi Zhong; Xuemiao Zhang; Ting Zeng; Limei Li; Gaojie Xu; Minhui Li; Jin Liu; Tai Yang

    NGF-TrkA is well known to play a key role in propagating and sustaining pruritogenic signals, which form the pathology of chronic pruritus. Inhibition of NGF-TrkA is a known strategy for the treatment of pruritus. In the present paper, we describe the identification, in vitro characterization, structure–activity analysis, and inhibitory evaluation of a novel TrkA inhibitory scaffold exemplified by Cucurbitacins (Cus). Cus were identified as TrkA inhibitors in a large-scale kinase library screen. To obtain structural models of Cus as TrkA inhibitors, AutoDock was used to explore their binding to TrkA. Furthermore, PC12 cell culture systems have been used to study the effects of Cus and traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) extracts on the kinase activity of TrkA. Cus block the phosphorylation of TrkA on several tyrosine sites, including Tyr490, Tyr674/675, and Tyr785, and inhibit downstream Akt and MAPK phosphorylation in response to NGF in PC12 cell model systems. Furthermore, traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) containing Cu extracts were shown to inhibit the phosphorylation of TrkA and Akt. These data reveal mechanisms, at least partly, of the anti-pruritus bioactivity of Cus. Taken together, with the recent discovery of the important role of TrkA as a therapeutic target, Cus could be the basis for the design of improved TrkA kinase inhibitors, which could someday help treat pruritus.

    更新日期:2019-11-28
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
中国科学院微生物研究所潘国辉
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug