Oleanolic acid ameliorates collagen induced arthritis in rats through the gut microbiota

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis, synovium hyperplasia and destruction of cartilage and bone. Oleanolic acid (OA), one of the pentacyclic triterpenoids widely found in crude drugs, fruits and vegetable, shows an excellent anti-inflammatory ability. However, its effect on RA and the underlying mechanisms is still unclear. In this study, the effect of OA on the collagen – induced arthritis (CIA) in rats were investigated. Oral administration of OA (100 mg/kg) reduced the clinical signs and joint destruction of CIA rats, as well as marked down regulated the frequency of Th17 cell and up regulated the frequency of Treg cell in mesentery. In contrast, an intravenous injection of OA failed to affect the arthritis in rats, implying that its anti-arthritic effect was gastrointestinal tract-dependent. Further studies revealed that oral OA alleviated CIA in a gut microbiota-dependent manner. OA had no effect on the diversity and richness of the gut bacteria, but reduced the abundance of Prevotella in CIA rats as determined by the 16S rRNA gene sequence. While the co-administration of broad-spectrum antimicrobials largely diminished the antiarthritic effect of OA. In conclusion, the research suggested that OA, which regulated the intestinal micro-environment, could be used as a potential component to treat RA.