Experimental study of Forsythoside A on prevention and treatment of avian infectious bronchitis

doi:10.1016/j.rvsc.2020.11.009

Research in Veterinary Science

Volume 135, March 2021, Pages 523-531

https://doi.org/10.1016/j.rvsc.2020.11.009 Get rights and content

Abstract

Forsythoside A is the main active ingredient in the Chinese medicine Forsythia suspensa, which has antiviral, anti-inflammatory, antioxidation, and immunoregulatory effects. It is reported that Forsythoside A can significantly inhibit the replication of the avian infectious bronchitis virus(IBV) in cells, but there is no report in chickens. The present study aimed to investigate the effect of Forsythoside A on IBV-M41, experiments were designed using 120 chickens at 12 days of age. The chickens were randomly divided into eight groups: Forsythoside A high-, medium-, and low-dose prevention groups, Forsythoside A high-, medium-, and low-dose treatment groups, model control group and normal control group. All chickens, except the normal control group, were inoculated with 0.2 ml of IBV-M41 at 15 days of age.The antiviral effects were evaluated by clinical signs, weight, histopathology, T-,B-lymphocyte proliferation, T-lymphocyte subsets and cytokine levels.The results showed that the infection rate in each Forsythoside A prevention group was significantly lower than that in the treatment group and model control group (P < 0.05). The recovery rate in each Forsythoside A treatment group was significantly higher than that in the model control group (P < 0.05), and the recovery rate in high- and medium-dose treatment group was the highest, at up to 86.67%. Lymphocytic transformation ability significantly improved in the prevention and treatment groups. Forsythoside A significantly improved the CD3+, CD4+, and CD8+ T-lymphocyte of infected chickens. The cytokine level was able to maintain high concentrations of IL-2 and IFN-α for a long time and maintain a dynamic IL-4-concentration balance. A number of results showed that Forsythoside A had both preventive and therapeutic effects in IBV-M41-infected chickens, among which the high-dose (80 mg/kg/d) prevention group，the high- (80 mg/kg/d) and medium (40 mg/kg/d) -dose treatment group had significant effects.

Introduction

Infectious bronchitis (IB) is an acute and highly contagious respiratory disease of chickens that is caused by the avian infectious bronchitis virus (IBV)(Cavanagh, 2007; Cavanagh et al., 2008). In chickens, IBV infections often develop associated diseases and secondary infection, such as newcastle disease, chronic respiratory disease, and some bacterial infections. Similar to the coronaviruses, IBV diversifies quickly through spontaneous mutation and gene recombination (Sjaak et al., 2011). There are many serotypes of IBV with each strain having a different virulence. A minimal degree of cross-protection between strains means that IBV vaccination has little effect, and chickens with immunity commonly become re-infect(Balestrin et al., 2014). These problems mean that the prevention and control of IBV infection are very difficult. IBV infection reduces not only the productivity of broilers but also the egg quality and productivity of laying hens. Outbreaks of IBV infection can cause enormous economic losses to the poultry industry(Britton et al., 2012).

Forsythoside A is the main active ingredient in the Chinese medicine Forsythia suspensa, which has antiviral(Deng et al., 2016; Law et al., 2017), anti-inflammatory(Cheng et al., 2014; Zhang et al., 2018), antioxidation(Yuan et al., 2016), and immunoregulatory(Zhang et al., 2013) effects. Recent studies have shown that Lianhuaqingwen, which mainly consists of Forsythia suspensa, can significantly inhibit the replication of SARS-CoV-2 in Vero E6 cells and reduce the expression of the proinflammatory cytokines TNF-α, IL-6, CCL-2/MCP-1, and CXCL-10/IP-10(Li et al., 2020). Forsythoside A can significantly inhibit the replication of IBV in cells(Li et al., 2011) while activating the intracellular receptors MDA5, LGP2, and NLRC5, which further activate the downstream expression of the antiviral genes IRF7, IFN-α, and IFN-β (Zhang et al., 2017). However, the effect of Forsythoside A on infectious bronchitis in chickens has not been reported. The purpose of our study was to investigate whether Forsythoside A has any antiviral effects against IBV by establishing a model IBV-infected chicken. By evaluating the effects of Forsythoside A treatment, we aimed to reveal the potential mechanisms of how Forsythoside A acts on IBV.

Section snippets

Virus

The IBV-M41 standard strain (No. AV1511) was purchased from the Chinese Veterinary Drug Administration. In our previous study, we found that the EID₅₀/0.1 ml of the virus on chicken embryos was 10^–6.32. In our IBV-M41 chicken model, we used the infective dose 10⁵EID₅₀.

Animals

One-day-old AA white-feather broilers were purchased from Kaifeng Xingda Poultry Co., Ltd. in Henan Province. The chickens were conventionally raised for 12 days without any vaccination before being used in the experiments. The

Clinical efficacy

The infection rate in each Forsythoside A prevention group was significantly lower than that in the treatment group and model control group (P < 0.05). The recovery rate in each Forsythoside A treatment group was significantly higher than that in the model control group (P < 0.05), and the recovery rate in high- and medium-dose treatment group was the highest, at up to 86.67%. (Table 1).

Productivity

There was no significant difference in the feed conversion ratio for days 1–12 in each group. For days 12–22

Discussion

This study verified that Forsythoside A has prevention and treatment effects on IBV infection in chickens. Compared with the model control group, the mental state, respiratory symptoms, feed intake and activities of Forsythoside A-treated chickens improved during the study period. The recovery of Forsythoside A-treated chickens regained earlier and faster than the model control group. Chickens from the model control group exhibited pathological changes, such as a lot of hemorrhaging or

Funding

This work was financially supported by Henan Academy of Sciences Research and development Project (190413008).

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author contributions

All authors made substantial contributions to the design and conception; acquisition, analysis or interpretation of data. Authors took part in either drafting or revising the manuscript. At the same time, authors gave final approval of the version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of Competing Interest

The authors declare that they have no competing interests.

Acknowledgment

Not applicable.

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Review of the therapeutic potential of Forsythiae Fructus on the central nervous system: Active ingredients and mechanisms of action
2024, Journal of Ethnopharmacology
Traditional Chinese medicine has gained significant attention in recent years owing to its multi-component, multi-target, and multi-pathway advantages in treating various diseases. Forsythiae Fructus, derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is one such traditional Chinese medicine with numerous in vivo and ex vivo therapeutic effects, including anti-inflammatory, antibacterial, and antiviral properties. Forsythiae Fructus contains more than 200 chemical constituents, with forsythiaside, forsythiaside A, forsythiaside B, isoforsythiaside, forsythin, and phillyrin being the most active ingredients. Forsythiae Fructus exerts neuroprotective effects by modulating various pathways, including oxidative stress, anti-inflammation, NF-κB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARγ signaling pathway.
This review aims to highlight the potential therapeutic effects of Forsythiae Fructus on the central nervous system and summarize the current knowledge on the active ingredients of Forsythiae Fructus and their effects on different pathways involved in neuroprotection.
In this review, we conducted a comprehensive search of databases (PubMed, Google Scholar, Web of Science, China Knowledge Resource Integrated, local dissertations and books) up until June 2023 using key terms such as Forsythia suspensa, Forsythiae Fructus, forsythiaside, isoforsythiaside, forsythin, phillyrin, Alzheimer′s disease, Parkinson's disease, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, aging, and herpes simplex virus encephalitis.
Our findings indicate that Forsythiae Fructus and its active ingredients own therapeutic effects on the central nervous system by modulating various pathways, including oxidative stress, anti-inflammation, NF-κB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, the gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARγ signaling pathway.
Forsythiae Fructus and its active ingredients have demonstrated promising neuroprotective properties. Future in vivo and clinical studies of Forsythiae Fructus and its active ingredients should be conducted to establish precise dosage and standard guidelines for a more effective application in the treatment of neurological disorders.
Radix Isatidis polysaccharide (RIP) resists the infection of QX-type infectious bronchitis virus via the MDA5/TLR3/IRF7 signaling pathway
2023, Poultry Science
Although vaccines play a major role in the prevention of infectious bronchitis (IB), Anti-IB drugs still have great potential in poultry production. Radix Isatidis polysaccharide (RIP) is a crude extract of Banlangen with antioxidant, antibacterial, antiviral, and multiple immunomodulatory functions. The aim of this study was to explore the innate immune mechanisms responsible for RIP-mediated alleviation of infectious bronchitis virus (IBV)-induced kidney lesions in chickens. Specific-pathogen-free (SPF) chicken and chicken embryo kidney (CEK) cells cultures were pretreated with RIP and then infected with the QX-type IBV strain, Sczy3. Morbidity, mortality, and tissue mean lesion scores were calculated for IBV-infected chickens, and the viral loads, inflammatory factor gene mRNA expression levels, and innate immune pathway gene mRNA expression levels in infected chickens and CEK cell cultures were determined. The results show that RIP could alleviate IBV-induced kidney damage, decrease CEK cells susceptibility to IBV infection, and reduce viral loads. Additionally, RIP reduced the mRNA expression levels of the inflammatory factors IL-6, IL-8, and IL-1β by decreasing the mRNA expression level of NF-κB. Conversely, the expression levels of MDA5, TLR3, STING, Myd88, IRF7, and IFN-β were increased, indicating that RIP conferred resistance to QX-type IBV infection via the MDA5, TLR3, IRF7 signaling pathway. These results provide a reference for both further research into the antiviral mechanisms of RIP and the development of preventative and therapeutic drugs for IB.
Virtual screening and molecular dynamics simulation analysis of Forsythoside A as a plant-derived inhibitor of SARS-CoV-2 3CLpro
2022, Saudi Pharmaceutical Journal
Citation Excerpt :
Because these are natural compounds in the selected dataset having large chemical structures, So ADMET parameters usually violate but as the molecular docking results are promising, the selected lead compound have generated 6 HBs and very notable binding energy (-8.6225 kcal/mol) and presented interacts with the significant residues of the active site (Fig. 3). Lead compound’s medicinal status is confirmed from the literature also and founds effective with respect to potential anti-viral drugs for avian infections of bronchitis virus (Li et al., 2011; Wang et al., 2021), influenza virus (Law et al., 2017), and CoV (Bailly, 2021). Some recent studies highlight the importance of our selected lead compound “Forsythoside A” an active chemical isolated from Forsythia suspense and famous for different pharmacological activities and most commonly used traditional antiviral medicine (Bailly, 2021).
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a more severe strain of coronavirus (CoV) that was first emerged in China in 2019. Available antiviral drugs could be repurposed and natural compounds with antiviral activity could be safer and cheaper source of medicine for SARS-CoV-2. 78 natural antiviral compounds database was identified from literature and virtual screening technique was applied to identify potential 3-chymotrypsin-like protease (3CLpro) inhibitors. Molecular docking studies were conducted to analyze the main protease (3CLpro) and inhibitors interactions with key residues of active site of target protein (PDB ID: 6LU7), active site constitute the part of active domain I and II of 3CLpro. 10 compounds with highest dock score were subjected to calculate ADMET parameters to figure out drug-likeness. Molecular dynamic (MD) simulation of the selected lead was performed by Amber simulation package to understand the conformational changes in docked complex. MD simulations analysis (RMSD, RMSF, Rg, BF, HBs, and SASA plots) of lead bounded with 3CLpro, hence revealed the important structural turns and twists during MD simulations from 0 to 100 ns. MM-PBSA/GBSA methods has also been applied for the estimation binding free energy (BFE) of the selected lead-complex. The present study has identified lead compound “Forsythoside A” an active extract of Forsythia suspense as SARS-CoV-2 3CLpro inhibitor that can block the viral replication and translation. Structural analysis of target protein and lead compound performed in this study could contribute to the development of potential drug against SARS-CoV-2 infection.
Forsythiaside A alleviated carbon tetrachloride-induced liver fibrosis by modulating gut microbiota composition to increase short-chain fatty acids and restoring bile acids metabolism disorder
2022, Biomedicine and Pharmacotherapy
Citation Excerpt :
Forsythoside A (FTA, Fig. 1) is the main active component isolated from FF and has prominent bioactivities. Modern pharmacological studies have confirmed that FTA shows significant activity in the treatment of various diseases, including inflammation [6,7], viral infection [8], cerebral ischemia [9], and bronchitis [10]. As reported, FTA could alleviate acetaminophen-induced liver injury by regulating ECM remodeling and phosphatidylinositol 3 kinase/protein kinase B-mediated apoptosis in zebrafish [11].
Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated from the traditional Chinese medicine Forsythiae Fructus (Lian Qiao), is a natural hepatoprotective agent. The purpose of this study was to investigate the protective effect of FTA on carbon tetrachloride (CCl₄)-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2 mL/kg CCl₄ three times a week for 4 weeks. FTA attenuated CCl₄-induced liver fibrosis in mice, which was proved by the results of Masson and Sirius red staining, liver hydroxyproline, hyaluronic acid, laminin, type III procollagen, and type IV collagen assays. FTA inhibited hepatic stellate cell activation, and reduced hepatic inflammation and oxidative stress in mice treated with CCl₄. What’s more, FTA ameliorated CCl₄-induced gut dysbiosis, maintained intestinal barrier function, increased the production of short-chain fatty acids (SCFAs), and improved endotoxemia, as manifested by decreased serum lipopolysaccharide levels and increased expression of ileal tight junction proteins. Besides, FTA can modulate the genes related to bile acid metabolism to alter the distribution of fecal BAs in fibrotic mice. In a word, FTA can improve liver fibrosis by inhibiting inflammation and oxidative stress, regulating gut microbiota and BA metabolism, and increasing the content of SCFAs. The results of this study provided an important reference for the study on the mechanisms by which natural products prevent liver fibrosis.
A review of pharmacological and pharmacokinetic properties of Forsythiaside A
2021, Pharmacological Research
Citation Excerpt :
According to reports, Forsythiaside A (40, 80 mg/kg/day) dramatically improved the clinical symptoms and mental state of chickens infected with bronchitis virus, alleviated lung and trachea injury, and enhanced the antiviral response ability [101]. The results indicated that Forsythiaside A could exert antiviral effect through modulating the immune functions, as evidenced by the improved CD3+, CD4+, and CD8+ T-lymphocyte of the infected chickens, the increased expressions of IL-2 and IFN-α, and the balance of dynamic IL-4-concentration [101]. Inflammatory response and oxidative stress are recognized as key events during the development of neurodegenerative diseases [24,102].
Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Forsythiae Fructus, the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a widely used Chinese medicinal herb in clinic for its extensive pharmacological activities. Forsythiaside A is the main active index component isolated from Forsythiae Fructus and possesses prominent bioactivities. Modern pharmacological studies have confirmed that Forsythiaside A exhibits significant activities in treating various diseases, including inflammation, virus infection, neurodegeneration, oxidative stress, liver injury, and bacterial infection. In this review, the pharmacological activities of Forsythiaside A have been comprehensively reviewed and summarized. According to the data, Forsythiaside A shows remarkable anti-inflammation, antivirus, neuroprotection, antioxidant, hepatoprotection, and antibacterial activities through regulating multiple signaling transduction pathways such as NF-κB, MAPK, JAK/STAT, Nrf2, RLRs, TRAF, TLR7, and ER stress. In addition, the toxicity and pharmacokinetic properties of Forsythiaside A are also discussed in this review, thus providing a solid foundation and evidence for further studies to explore novel effective drugs from Chinese medicine monomers.
Forsythoside A inhibits apoptosis and autophagy induced by infectious bronchitis virus through regulation of the PI3K/Akt/NF-κB pathway
2023, Microbiology Spectrum

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¹: These authors contributed equally to this work

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Experimental study of Forsythoside A on prevention and treatment of avian infectious bronchitis

Abstract

Introduction

Section snippets

Virus

Animals

Clinical efficacy

Productivity

Discussion

Funding

Availability of data and material

Author contributions

Declaration of Competing Interest

Acknowledgment

J. Poult. Sci.

J. Ethnopharmacol.

Poult. Sci.

J. Immunity.

J. Molecules.

J. Int. Immunopharmacol.

Cytokines: coordinators of immune and inflammatory responses

J. Annu Rev Biochem.

Role of interferons and other cytokines in the regulation of the immune response

J. APMIS.

Modification of the avian coronavirus infectious bronchitis virus for vaccine development

J. Bioeng. Bugs.

Coronavirus avian infectious bronchitis virus

J. Vet. Res.

Infectious bronchitis

Forsythiaside attenuates lipopolysaccharide-induced inflammatory responses in the bursa of Fabricius of chickens by downregulating the NF-κB signaling pathway

J. Exp. Ther. Med.