Cyasterone alleviates collagen-induced arthritis in mice by activating autophagy and inhibiting inflammation via the TLR4/MyD88/NF-κB signaling pathway

doi:10.5246/jcps.2026.05.031

Abstract

Abstract:

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Cyasterone, a phytoecdysteroid, demonstrates anti-inflammatory potential, but its mechanism in RA remains unclear. This study aims to investigate Cyasterone’s therapeutic effect and underlying mechanisms in collagen-induced arthritis (CIA) mice. Cell migration and cell invasion capabilities were measured by the transwell assay. Apoptosis was detected by TUNEL or flow cytometry. Tail vein injection of bovine type II collagen was used to establish the mouse CIA model. The enzyme-linked immunoassay was performed to measure inflammatory factor concentrations. Quantitative real-time PCR or WB analysis was performed to detect gene or protein expression. CIA was assessed by the arthritis index and claw thickness curve, etc. The results demonstrated that Cyasterone had dose-dependent inhibitory effects on the proliferation, migration, and invasion of rheumatoid arthritis-fibroblast like synoviocytes (RA-FLS). Cyasterone increased apoptosis and reduced inflammation in RA-FLS, indicating its protective effects in RA. Cyasterone inhibited TLR4/MyD88/NF-κB pathway and increased autophagy in RA-FLS, as demonstrated by reduced TLR4, MyD88, phosphorylated p65, and p-mTOR levels while increasing Beclin 1 expression and light chain 3 II/I ratio. The in vivo results further confirmed that Cyasterone reduced the arthritis index and paw swelling, significantly reduced the serum levels of inflammatory factors, alleviated synovial hyperplasia and destruction of cartilage structure, demonstrating an anti-cartilage damage effect. In conclusion, Cyasterone protected against CIA through the TLR4/MyD88/NF-κB signaling pathway, which might be a promising candidate for arthritis treatment.

Key words: Arthritis, Cyasterone, Fibroblast-like synoviocytes, TLR4/MyD88/NF-κB signaling pathway, Inflammation

Supporting: /attached/file/20260529/20260529192238_479.pdf

Xinfang Tan, Yuan Liu, Pengbo Shi, Jiangtao Ma, Chengxi Huang, Zhifang Wu, Xiaoshen Hu, Liangliang Xu. Cyasterone alleviates collagen-induced arthritis in mice by activating autophagy and inhibiting inflammation via the TLR4/MyD88/NF-κB signaling pathway[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(5): 438-453.

Figures/Tables 6

References 54

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