Lamiophlomis rotata attenuates rheumatoid arthritis by regulating sphingolipid and steroid hormone metabolism

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease. Lamiophlomis rotata (L. rotata) (Benth.) Kudo, an essential medicinal plant in traditional Tibetan medicine, is useful in treating RA. The purpose of this study was to evaluate L. rotata's anti-RA effect and to analyze its serum metabolites and lipids to predict the possible action pathways. Female and male rats were immunized with CFA to induce arthritis. Paw volumes were measured, and arthritis index analysis and histological analysis were performed to check the effects of L. rotata. ELISA was used to measure the levels of inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-10) and oxidative stress (MDA, SOD, GSH, and CAT). UPLC/Q-Orbitrap-MS was used to identify untargeted metabolites and lipids in serum. Metabolite validation was performed using UPLC/QQQ-MS. L. rotata application significantly reduced arthritis indices and paw swelling in AIA rats, and diminished inflammation and bone fractures in joint tissues. Sphingolipid (SP) and steroid hormone biosynthesis was found to be closely related to L. rotata's intervention in RA. In addition, our experiments also confirmed that females were more likely than males to develop RA. These findings provide clues and a scientific basis for the mechanism of L. rotata in treating RA.