Oleanolic acid ameliorates collagen induced arthritis in rats through the gut microbiota
Chipu Liu1, Yue Zhao1, Xiaoran Su1,2
1Department of Pharmacology, Hebei University of Chinese Medicine, No. 326 South Xinshi Road, Shijiazhuang, 050091, Hebei, China.
Objectives:
Oleanolic acid (OA) is a natural anti-inflammatory triterpenoid. This study investigates its therapeutic potential against rheumatoid arthritis (RA), a chronic autoimmune condition characterized by inflammatory activity, and explores the novel mechanism of gut microbiota modulation in a rat model.
Methods:
The anti-arthritic effect of OA was assessed in collagen-induced arthritis (CIA) in rats following oral or intravenous administration. Arthritis severity, joint pathology, and mesenteric Th17/Treg cell frequencies were evaluated. The role of gut microbiota was investigated using 16S rRNA sequencing and antibiotic ablation.
Key Findings:
Oral, but not intravenous, OA administration significantly alleviated arthritis and joint damage in CIA rats, indicating a gastrointestinal-dependent mechanism. Therapeutically, oral OA modulated gut microbiota by reducing Prevotella abundance and restored immune balance by decreasing Th17 and increasing Treg cell frequencies. This protective effect was abolished by co-treatment with antibiotics, confirming gut microbiota-dependency.
Conclusions:
Taken together, our findings show that the improvement in CIA after oral administration of OA is mainly due to changes in the structure and function of the gut microbiota. This study, therefore, suggests that OA is a promising therapeutic candidate for RA, based on its ability to restore the intestinal microenvironment.
Insights
Oleanolic acid shows therapeutic potential for rheumatoid arthritis by modulating gut microbiota. Oral administration reduced inflammation and restored immune balance, suggesting a promising treatment strategy.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by inflammation.
- Oleanolic acid (OA) is a natural anti-inflammatory compound.
Purpose of the Study:
- To investigate the therapeutic potential of OA against RA.
- To explore OA's mechanism of action involving gut microbiota modulation.
Main Methods:
- Collagen-induced arthritis (CIA) rat model.
- Oral and intravenous OA administration.
- 16S rRNA sequencing and antibiotic ablation to assess gut microbiota role.
Main Results:
- Oral OA significantly reduced arthritis severity and joint damage in CIA rats.
- OA modulated gut microbiota, decreasing Prevotella and restoring Th17/Treg cell balance.
- Antibiotic treatment abolished OA's protective effects, confirming gut microbiota dependency.
Conclusions:
- Oral OA's anti-arthritic effects are mediated by gut microbiota modulation.
- OA shows promise as a therapeutic agent for RA by restoring intestinal microenvironment.
