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The Effect of Resveratrol in Sirt1/CST Pathway to Inhibit TNF-α Induced Inflammatory Response in Rat Primary
Xu-Meng Chen1, Yi-Jie Guo1, Hui-Wen Ling1
1School of Pharmacy, Hunan University of Chinese Medicine.
Abstract:
Rheumatoid arthritis has a significant impact on the life quality, but current pharmacological therapies have limitations. As a result, there is growing interest in exploring the potential of natural plant components to intervene in the development of rheumatoid arthritis. Resveratrol, a natural polyphenol and one of the main active components of the Chinese herbal medicine Polygonum cuspidatum, has emerged as a promising candidate for this purpose. In the present study, we investigated the role and mechanism of resveratrol in inhibiting inflammatory response in rat primary fibroblast-like synoviocytes. Tumor necrosis factor (TNF)-α was used to establish a model of inflammation, the Sirtuin1 selective inhibitor Selisistat (EX527) was used to inhibit Sirtuin1 activity, and small interfering RNA was used to silence cortistatin expression. The results showed that pre-treatment with resveratrol could time- and dose-dependently inhibit TNF-α induced cellular interleukin (IL)-1β and IL-6 secretion, and upregulate Sirtuin1 and cortistatin mRNA and protein expression in the range of 48 h, 100 µM. Selisistat (EX527) could attenuate resveratrol inhibited inflammatory response and upregulated cortistatin expression. Silencing cortistatin expression attenuated the effect of resveratrol on inhibiting inflammatory response, but did not affect its effect on upregulating Sirtuin1 expression. In conclusion, resveratrol effectively inhibited the TNF-α induced inflammatory response in fibroblast-like synoviocytes by a mechanism involving the Sirtuin1/cortistatin pathway.
Insights
Resveratrol, a natural compound, effectively reduces inflammation in rheumatoid arthritis fibroblast cells. It works by activating the Sirtuin1/cortistatin pathway, offering a potential natural therapy for the condition.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Rheumatoid arthritis significantly impacts quality of life, with current treatments having limitations.
- Natural compounds like resveratrol are being explored for their therapeutic potential in rheumatoid arthritis.
- Resveratrol, derived from Polygonum cuspidatum, is a promising polyphenol for intervention.
Purpose of the Study:
- To investigate the role and mechanism of resveratrol in inhibiting inflammatory responses.
- To examine resveratrol's effect on fibroblast-like synoviocytes in a rheumatoid arthritis model.
- To elucidate the involvement of the Sirtuin1/cortistatin pathway in resveratrol's anti-inflammatory action.
Main Methods:
- Utilized rat primary fibroblast-like synoviocytes.
- Induced inflammation using Tumor Necrosis Factor-alpha (TNF-α).
- Employed Sirtuin1 inhibitor (Selisistat/EX527) and cortistatin small interfering RNA (siRNA) for mechanistic studies.
Main Results:
- Resveratrol inhibited TNF-α-induced Interleukin (IL)-1β and IL-6 secretion in a time- and dose-dependent manner.
- Resveratrol upregulated Sirtuin1 and cortistatin mRNA and protein expression.
- Inhibition of Sirtuin1 or cortistatin attenuated resveratrol's anti-inflammatory effects, confirming pathway involvement.
Conclusions:
- Resveratrol demonstrates significant anti-inflammatory effects in fibroblast-like synoviocytes.
- The mechanism involves the upregulation of the Sirtuin1/cortistatin pathway.
- Resveratrol presents a potential natural therapeutic agent for managing rheumatoid arthritis inflammation.
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