Wutou decoction attenuates rheumatoid arthritis in rats through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway

• Published in: Journal of ethnopharmacology 2025-01, Vol.337 (Pt 3), p.118921, Article 118921
• Main Authors: Shen, Pan, Lin, Weiji, Huang, Yao, Ba, Xin, Han, Liang, Li, Tingting, Qin, Kai, Chen, Zhe, Tu, Shenghao
• Format: Article
• Language: English
• Subjects: Acetylation; animal models; Animals; Anti-Inflammatory Agents - pharmacology; Arthritis, Experimental - drug therapy; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - drug therapy; cell viability; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; fluorescent antibody technique; High-mobility group box 1; histopathology; HMGB1 Protein - metabolism; interleukin-6; macrophages; Male; micro-computed tomography; NF-kappa B - metabolism; NF-κB; nucleoproteins; Oriental traditional medicine; Rats; RAW 264.7 Cells; Rheumatoid arthritis; Signal Transduction - drug effects; Silent information regulator 1; Sirtuin 1 - metabolism; therapeutics; Western blotting; Wutou decoction
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118921

In traditional Chinese medicine (TCM), Wutou Decoction (WTD) has long been used to alleviate arthritis. Emerging studies have reported that WTD could improve the symptoms of rheumatoid arthritis (RA). However, the mechanism by which WTD is involved in the treatment of RA remains elusive, posing a challenge to the worldwide acceptance of WTD as an efficient RA therapy. This study investigated the antiarthritic efficacy of WTD in a collagen-induced arthritis (CIA) rat model and explored silent information regulator 1 (SIRT1)-mediated deacetylation of the high mobility group box 1 (HMGB1)/NF-κB pathway. A rat CIA model was used to evaluate the antiarthritic activity of WTD. Clinical arthritis score assessment, left ankle thickness assessment, micro-CT, histopathological staining, immunofluorescence staining, and ELISA were conducted to elucidate the anti-inflammatory effects of WTD. The M1 macrophage polarization state, cell viability, and invasion were also determined to assess the effects of WTD on macrophage proliferation and invasion in vitro. Additionally, in vivo and in vitro HMGB1 nuclear translocation and NF-κB activation were analysed. Finally, deacetylase activity was assessed by Western blot, NAD+/NADH analysis, and co-immunoprecipitaion. WTD significantly alleviated arthritis in CIA rats and inhibited pathological changes in joint lesions while concurrently suppressing TNF-α, IL-6, and IL-1β release. Mechanistically, WTD suppressed M1 infiltration in ankle tissues and their invasion in vitro. Furthermore, WTD downregulated HMGB1/p65 nuclear translocation and acetylation, which may be associated with SIRT1 upregulation. Overall, WTD potentially alleviates RA through SIRT1-mediated downregulation of HMGB1 and NF-κB acetylation. [Display omitted] •WTD alleviated synovial inflammation and joint damage in RA rats.•WTD exerted a significant downregulation of HMGB1 acetylation by enhancing SIRT1 activity.•The modulation of WTD resulted in the inhibition of HMGB1 nucleocytoplasmic translocation, effectively sequestering HMGB1-mediated activation of the NF-κB pathway.•The results provided a scientific explanation for the theory of the anti-arthritic effects by WTD of Quxie and Fuzheng.