Inhibitory effect of Salvia coccinea on inflammatory responses through NF-κB signaling pathways in THP-1 cells and acute rat diabetes mellitus

https://doi.org/10.1016/j.acthis.2021.151735Get rights and content

Abstract

Hyperglycemia-induced oxidative stress has been implicated in diabetes and its complications. Medicinal plants possessing antioxidant activity may decrease oxidative stress by scavenging radicals and reducing power activity and would be a promising strategy for the treatment of inflammatory disorders like diabetes. This study was designed to evaluate the antioxidant effect of Aqueous Extract of  S.coccinea leaf (AESL) in HG treated THP-1 cells and streptozotocin (STZ)-induced diabetic Wistar rats. AESL and the standard antidiabetic drug glibenclamide were administered orally by intragastric tube for 14 days and pre-treated HG grown THP-1 cells. AESL treatment reduced HG induced increase in ROS production, NF-κB dependent proinflammatory gene expression by influencing NF-κB nuclear translocation in THP-1 cells. Oral administration of AESL inhibited STZ-induced increase in serum lipid peroxidation, aspartate transaminase, alanine transaminase, and Lactate dehydrogenase of diabetic rats. Significant increase in activity of superoxide dismutase, catalase and glutathione peroxidase, and a reduced level of glutathione, were observed in AESL treatment. The results demonstrate that AESL is useful in controlling blood glucose and also has antioxidant potential to influence the translocation of NF-κB, protect damage caused by hyperglycemia-induced inflammation.

Introduction

Inflammation is one among the basic entities of both physiological and pathological processes. A number of chronic life-threatening diseases, including diabetes, cardiovascular diseases and arthritis have inflammation as the pathophysiologically important component (Okin and Medzhitov, 2012). Perturbance of the link between metabolism and immune system characterizes diabetes as an inflammatory disease (Pahwa and Jialal, 2019). Oxidative stress has been implicated in the pathogenesis of several diseases such as diabetes mellitus. In diabetes mellitus, chronic hyperglycemia condition produces multiple biochemical sequels and hyperglycemia induced oxidative stress play an important role in the onset and progression of the diseases (Banday et al., 2020).

The coordinated balance between oxidant and anti-oxidant machinery regulate ROS production. Unlike moderate level ROS, which required for the maintenance of cellular homeostasis signaling through wide spectrum of pathways and regulating key transcription factors, excessive ROS generation lead to the production of various inflammatory mediators and progression of inflammatory tissue damage (Checa et al., 2020; Mittal et al., 2014). Hyperglycemia induced reactive oxygen species (ROS) production activates four major pathways such as superoxide overproduction, indirect activation of Advanced glycation end products (AGEs), protein kinase C (PKC) and the hexosamine pathway; interrupting ROS production modifies these four pathways (Busik et al., 2008). This hyperglycemia produced ROS will disrupt the redox balance cause inflammation and tissue damage. (Shanmugam et al., 2004). Monocytes are orchestrator of inflammatory response and play key role in the development of inflammatory disease (Rachel et al., 2017). Exposure of inflammatory stimuli activates the first line of defense cell monocytes for ROS production (Gordon, 1998). When monocyte submerged in high glucose (HG) as seen in diabetes mellitus, activate the cell to produce immune cell responses. Inflamed cells produce and secrete inflammatory protein like Cyclooxygenase (COX)-2, inflammatory cytokines Monocyte Chemoattractant Protein (MCP-1), Tumor necrosis factor (TNF)-α and Interleukin (IL)-6, IL-17E, IL-17C, and chemokine IFN-γ–inducible protein (IP)-10, to develop inflammation (Chawla, 2011). ROS have been studied as the therapeutic targets for inflammatory disease progression and complications (Perillo et al., 2020). Thus, scavenging excessive ROS production and oxidative stress would be a promising strategy for the treatment of inflammatory disorders.

Traditional herbal medicine has been used to treat human diseases in India for centuries and plays a major role in the management of human health globally. Many plants have been used as food, medicine and perfumery. Naturally existing bioactive compounds from plants, including anti-oxidant compounds, are the main quarry for discovering new drug and useful to manage several disorders (Salehi et al., 2019)

Salvia L., largest genus in the Lamiaceae family of plants with nearly 1000 species including annual, biennial, or perennial herbs, along with woody subshrubs (Clebsch and Barner, 2003; Walker, 2004). Based on differences in corolla, calyx, and stamens, salvia is organized into twelve sections, placed in four subgenera. Many species of Salvia are similar to each other, and different specific names have been given to many species that have many varieties. Many species and varieties of Salvia have been used in folk medicine. For Salvia palaestina and S. ceratophylla were studied for their anti-oxidant activity, Salvia officinalis native to Middle East and Mediterranean was systematically analyzed for its antidiabetic, effect on experimental rat (Eidi and Eidi, 2009; Khattab et al., 2012). Salvia syriaca of Turkish origin and Salvia miltiorrhiza of China orgin were studied for their cardioprotective effect and vascular disorder such as atheriosclerosis, (BaoQing, 2010; Nickavar, 2007; Eidi and Eidi, 2009; Tepe et al., 2012; Ulubelen, 2003; Zhou et al., 2005; Andrade-Cetto, 2009). Salvia divinorum, used for it psychoactive properties (Brito-da-Costa et al., 2021) Very selective species of salvia were used to study for their biological (Eidi and Eidi, 2009; Khattab et al., 2012). However, systematic researches on the antioxidant and anti-inflammatory activities of S.coccinea, origin of India, still have not been carried out so far. The present study is a first attempt to evaluate anti-oxidant, anti-diabetic, anti-hyperlipidemic, and anti- inflammatory activities of aqueous extract of Indian S.coccinea leaf (AESL) in experimental animals and to identify the major compounds responsible for these activities. In this study, we found that the aqueous leaf extract from S.coccinea potently inhibits HG induced production of ROS, and the expression of inflammatory mediators, these effect are mediated, at least in part, via interfering NF-κB activation. Our results show that AESL possesses excellent antioxidant and anti-inflammatory activity and improves maintaining blood glucose level in STZ induced rats. Therefore, we believe that AESL is a natural material with excellent physiological activity and could be a candidate phytomedicine source for treating inflammatory diseases like diabetes.

Section snippets

Materials and methods

Streptozotocin, 2,2-diphenyl-1-picrylhydrazyl (DPPH), Bovine Serrum Albumin (BSA), 1,1,3,3-tetraethoxypropane, 3-(4,5-Dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT), were purchased from Sigma Chemicals, St. Louis, MO. Thiobarbituric acid was from Merck, Germany. RPMI-1640 medium, Pencillin-Streptomycin, Fetal Bovine Serum (FBS) were purchased from Gibco-Invitrogen. RNAeasy kit from Qiagen. RT-PCR primers were from Eurofins MWG; SYBR green QRT-PCR kit, lipofectamine 2000 were from

Preliminary in-vitro antioxidant activity and cell viability of AESL

Imbalance between oxidative and reduction in the body causes a state called Oxidative stress. Excessive generation of ROS is the cause of this imbalance, which in turn induces inflammatory mediators’ expression, leading to develop and progress inflammation (Hussain et al., 2016). Hence, scavenging excesses ROS in the cell can inhibit the damage caused by ROS, thereby prevent the development of inflammatory diseases. DPPH and free radical scavenging assays are universally used to assay the

Conclusions

AESL effectively eliminates free radicals and reactive oxygen species, significantly inhibits the expression of various inflammatory molecules, and at the same time down-regulates the activation of NF-κB signaling pathway by influence nuclear translocation, which denoting that AESL can effectively inhibit HG induced cell inflammation. AESL is a natural material with good anti- oxidant and anti-inflammatory activity. In addition, AESL significantly alleviated the rat`s diabetes mellitus, and

Authorship agreement

Authors have made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND

Author have drafted the work or revised it critically for important intellectual content; AND

Author have approved the final version to be published; AND

Author 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

Author contributions

Conceived and designed the experiments: NS. Performed the experiments: AS, GS: Analyzed the data: NS. Contributed reagents/materials/analysis tools: AS, GS: Wrote the paper: NS and AS.

Ethical approval

Approved by the Institutional Animal Ethical Committee of Bharathidasan University.

Informed consent

Not applicable.

Declaration of Competing Interest

The authors have declared that no conflict of interests exists.

Acknowledgements

This study was supported by grants from DST IndiaSR/SO/HS-2009, DBT IndiaBT/PR13260/BRB/10/754 and BT/PR12896/AGR/36/631 to SN. UGC India, BL/16-17/0484 to AS. The authors greatly acknowledge DST-PURSE, and DST-FIST to BMS, Bharathidasan University for instruments facility.

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