In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis

Abstract

Background: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti‐inflammatory, and immunomodulatory properties. </P><P> Objective: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. </P><P> Methods: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1β, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. </P><P> Results: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1β, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. </P><P> Conclusion: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.

Validating potent anti-inflammatory and anti-rheumatoid properties of Drynaria quercifolia rhizome methanolic extract through in vitro, in vivo, in silico and GC-MS-based profiling

“…In this regard, the known phyto-compounds of Withania somnifera has shown interaction with different cytokines in in silico docking and in vivo animal models and downregulated the expressions of iNOS, TNF-α, NF-κB etc. [ 68 , 69 ]. Compounds from Canabis sative and Prunella vulgaris also showed interactions with different cytokines in silico [ 68 ].…”

Indian Medicinal Plants and Formulations and Their Potential Against COVID-19–Preclinical and Clinical Research

“…W. somnifera formulation (supplemented with minerals) has been reported to improve both cellular and humoral immunity as well as hematological profile in addition to the significant inhibition in mouse splenocytes (Trivedi et al, 2017). Aqueous root extract of W. somnifera attenuates production of pro-inflammatory cytokines and transcription factor in collagen-induced arthritis (Khan et al, 2018). A study in 2018 showed that W. somnifera significantly inhibited mRNA expression of inflammatory cytokines and promotes the mRNA expression of the anti-inflammatory cytokine in HaCaT cells (Sikandan et al, 2018).…”

Withania somnifera (L.) Dunal: Opportunity for Clinical Repurposing in COVID-19 Management

“…WS aqueous extract along with fatty acids and withaferin A inhibited IL-6 and IL-1β released by monocytes, macrophages, and keratinocytes in vitro ( Balkrishna et al, 2020 ) ( Dubey et al, 2018 ) ( Neog et al, 2018 ) ( Sikandan et al, 2018 ). Withaferin A and WS aqueous extract significantly reduced serum levels of IL-1β and IL-6 secreted by bone marrow-derived dendritic cells and macrophages ( Morsy et al, 2019 ) ( Sultana etal., 2017 ) ( Noh et al, 2016 ) ( Kim et al, 2015 ) ( Khan et al, 2018 ). Withaferin A also suppressed IL-1β expression of the fibrotic lung of a mouse ( Bale et al, 2018a ).…”

“…Withaferin A ( Neog et al, 2018 ) ( Bale et al, 2018a ) and fatty acids of WS seeds ( Balkrishna et al, 2020 ) reduced NF-κB expression in monocytes, macrophages, and fibrotic lung tissues of mice. WS aqueous extract was found to inhibit NF-κB activation in collagen-induced arthritic rats ( Khan et al, 2018 ). The mechanistic studies revealed that NF-κB inhibition occurs due to the binding of withaferin A to the thiol group of cysteine residues ( Heyninck et al, 2014 ) ( Gambhir et al, 2015 ).…”