Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through Inhibiting TLR4/NF-κB/MAPK Pathway

Callicarpalongissima has been used as a Yao folk medicine to treat arthritis for years in China, although its active anti-arthritic moieties have not been clarified so far. In this study, two natural phenolic diterpenoids with anti-rheumatoid arthritis (RA) effects, rosmanol and carnosol, isolated from the medicinal plant were reported on for the first time. In type II collagen-induced arthritis DBA/1 mice, both rosmanol (40 mg/kg/d) and carnosol (40 mg/kg/d) alone alleviated the RA symptoms, such as swelling, redness, and synovitis; decreased the arthritis index score; and downregulated the serum pro-inflammatory cytokine levels of interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha (TNF-alpha). Additionally, they blocked the activation of the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappa B)/c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. Of particular interest was that when they were used in combination (20 mg/kg/d each), the anti-RA effect and inhibitory activity on the TLR4/NF-kappa B/MAPK pathway were significantly enhanced. The results demonstrated that rosmanol and carnosol synergistically alleviated RA by inhibiting inflammation through regulating the TLR4/NF-kappa B/MAPK pathway, meaning they have the potential to be developed into novel, safe natural combinations for the treatment of RA.

Automated summary

This study reported two natural phenolic diterpenoids, rosmanol and carnosol, isolated from Callicarpalongissima, which exhibited anti-rheumatoid arthritis (RA) effects. In a mouse model, both compounds alone improved RA symptoms and decreased arthritis index score. Moreover, they inhibited the production of pro-inflammatory cytokines and blocked the activation of specific signaling pathways. Of particular interest, the combination of these compounds showed enhanced anti-RA effects and inhibitory activity on the signaling pathway.