Isolated from Antrodia cinnamomea, 25S-antcin K suppresses the production of inflammatory cytokines and cartilage degradation in rheumatoid arthritis

Rheumatoid arthritis (RA) is a well-known autoimmune disorder associated with joint pain, swelling, cartilage and bone degradation, as well as deformity. In cellular and animal model investigations, extracts from Antrodia cinnamomea, a traditional medicinal fungus used in Taiwan, demonstrate anti-inflammatory properties. The 25(S) ergostane stereo-isomer of antcin K, known as 25S-antcin K, was previously isolated from A. cinnamomea and was found to exhibit a more potent effect than antcin K. In the current study, we examined the anti-RA effects of 25S-antcin K. 25S-antcin K abolishes IL-1β-induced promotion of TNF-α, CCL2, and VEGF arthritic factors production by inhibiting AMPK, Akt, and p38 pathways and enhancing miR-374b expression. Importantly, administration of 25S-antcin K also antagonizes collagen-induced arthritis-induced RA symptoms, such as inflammation, cartilage degradation, and bone erosion in vivo. These results provide a novel avenue, suggesting that 25S-antcin K is a potential candidate for developing RA therapy agents.