Triterpene saponins from Guo-gang-long attenuate collagen-induced arthritis via regulating A20 and inhibiting MAPK pathway

Ethnopharmacological relevance: The stems of Entada phaseoloides (L.) Merr commonly named Guo-gang-long, is a traditional Chinese folk medicine that has been used clinically in China for the treatment of arthritis. Our previous study described that triterpene saponins isolated from Guo-gang-long could inhibit the inflammatory response. However, the potential mechanism of Guo-gang-long on treatment of arthritis, and whether the triterpene saponins responsible for its anti-arthritic effect are unclear. Aim: To investigate the function and mechanisms of the triterpene saponins from E. phaseoloides (ES) in collageninduced arthritis (CIA) rats. Materials and methods: The chemical components of ES were analyzed by HPLC. Anti-arthritic activity of ES was investigated in CIA rats, which was established by immunization with bovine type II collagen. Three doses of ES (25, 50 and 100 mg/kg) were administrated using oral gavage to CIA rats daily for 3 weeks. The anti-arthritic activity of ES was evaluated by clinical arthritis scoring, paw swelling and mechanical sensitivity, as well as histological changes in CIA rats. The impacts of ES on the regulation of the ubiquintin-editing enzyme A20 and MAPK signaling pathway, and production of pro-inflammatory cytokines in CIA rats were examined by Western blot, quantitative real-time PCR, ELISA, and immunohistochemical staining, respectively. Results: ES treatment relieved the paw swelling, hyperalgesia and joint destruction, and prevented the progression of arthritis in CIA rats. Meanwhile, ES suppressed the excessive mRNA levels and protein expression of TNF-alpha and IL-17 in synovial tissues and hind paw joints, and reduced the production of IL-1 beta, TNF-alpha and IL-17 in serum. Furthermore, ES up-regulated A20 and suppressed the phosphorylation of p38 and ERK1/2 in hind paw joints, as well as inhibiting the activation of spinal p38 in CIA rats. Conclusion: ES could relieve rheumatic symptoms and prevent the development of rheumatoid arthritis. The effects of ES may be mediated by reducing proinflammatory cytokine levels, up-regulating A20 expression, reducing p38 and ERK1/2 activation in periphery, and inhibiting of phospho-p38 in spinal cord.

Automated summary

The triterpene saponins from Entada phaseoloides have been found to have therapeutic effects on collagen-induced arthritis in rats, reducing symptoms, decreasing the production of inflammatory cytokines, and inhibiting the MAPK signaling pathway, which ultimately prevents the progression of rheumatoid arthritis.