The Miao medicine Sidaxue alleviates rheumatoid arthritis in rats possibly by downregulating matrix metalloproteinases
10.12122/j.issn.1673-4254.2024.04.16
- VernacularTitle:苗药四大血减轻大鼠的类风湿性关节炎:基于下调基质金属蛋白表达
- Author:
Yunfei LI
1
;
Jingyi YANG
;
Ying ZHANG
;
Caixia ZHANG
;
Yuxiang WEI
;
Yiying WANG
;
Ning WU
;
Jianfei SUN
;
Zunqiu WU
Author Information
1. 贵州医科大学基础医学院化学与生物化学实验室,贵州 贵阳 561113
- Keywords:
Miao medicine Sidaxue formula;
rheumatoid arthritis;
matrix metalloproteinase;
matrix metalloproteinases;
network pharmacology;
cartilage and bone destruction
- From:
Journal of Southern Medical University
2024;44(4):739-747
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). Methods In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1β levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. Results Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1β, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. Conclusion Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1β/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.
