Chemical Composition and Anti-arthritic Potential of Himalayan Marmot Oil Against Type II Collagen-induced Rat Rheumatoid Arthritis

Background Animal-derived remedies are prominent in folk medicine worldwide, and discovering potent anti-inflammatory agents is attractive for rheumatoid arthritis (RA) treatment. Himalayan marmot oil (HMO), a traditional Tibetan medicine topically or orally used for burns and arthritis, has been common in Tibetan areas for centuries. However, the composition and systematic pharmacological evaluation of HMO are still unclear. Objectives This study focused on the chemical composition and anti-inflammatory effects of HMO in vitro and in vivo to expand the topical value of the application of HMO in RA. Materials and Methods First, the chemical composition of HMO was explored by gas chromatography–mass spectrometry (GC–MS). Then, we established a bioassay system for L929 cells and RAW 264.7 cells to evaluate the effect of HMO on cytotoxicity and inflammatory responses. The anti-arthritic evaluation involved testing for paw swelling, swelling inhibition, and histological analysis in collagen-induced arthritis (CIA) rats. Enzyme-linked immunosorbent assay, Western blot analysis, and quantitative real-time polymerase chain reaction were performed to determine the effect of HMO on the production and secretion of inflammatory cytokines. Results GC–MS results showed that seven categories of chemical substances, including 261 compounds in HMO, and the main components of HMO were saturated fatty acids and unsaturated fatty acids. HMO showed low toxicity in cells according to the CCK-8 tests. In CIA model rats, HMO obviously inhibited hind paw swelling and reduced the arthritis index. Pathological staining results and micro-CT imaging indicated that HMO attenuated synovial hyperplasia and inflammatory cell infiltration in joint tissues. Meanwhile, in vivo and in vitro , HMO significantly inhibited interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, while the expression of interleukin-10 (IL-10) was increased. Conclusion The current work identified an excellent anti-inflammatory animal-derived medicinal agent, HMO, in alleviating synovial inflammation and joint destruction by regulating IL-6, IL-10, and TNF-α expression with low toxicity, which provides a protective effect against RA. Our study expands the topical value of the application of HMO to inhibit the progression of inflammation, and it could be a safe, novel RA complementary therapy.