Ginsenoside metabolite compound K exerts anti-inflammatory and analgesic effects via downregulating COX2

Abstract

The present study aimed to evaluate the anti-inflammatory and analgesic activities of the ginsenoside metabolite compound K (CK) and its mechanisms. Mice model of xylene-induced ear swelling and rat model of carrageenan-induced paw swelling were used to evaluate the effect of CK on acute inflammation. The analgesic effect of CK was evaluated on heat-, acetic acid-, and carrageenan-induced hyperalgesia. The levels of prostaglandin E2 (PGE2), cyclooxygenase-1 (COX-1), and COX-2 in carrageenan-induced rat paw swelling and gastric mucosa were detected by enzyme-linked immunosorbent assay (ELISA). COX-1 and COX-2 expressions in carrageenan-induced rat paw swelling and gastric mucosa were detected by western blotting. In vitro effect of CK (10-9, 10-8, 10-7, 10-6, 10-5 M) on COX-1 and COX-2 activities was evaluated by measuring the production of 6-keto-PGF1α and PGE2 in rat peritoneal macrophages. CK at doses of 7, 14, 28, 56, 112, and 224mg/kg alleviated xylene-induced ear oedema, whereas CK at 40, 80, and 160mg/kg alleviated carrageenan-induced paw oedema. CK at 224mg/kg showed an analgesic effect against acetic acid-induced pain. CK at 40, 80, and 160mg/kg significantly increased rat inflammatory pain threshold, but had no effect on heat-induced pain threshold. CK at 10, 20, 40, 80, and 160mg/kg reduced PGE2 level in the paw tissue, but showed no effect on that in the gastric mucosa. CK at 20, 40, 80, and 160mg/kg decreased COX-2 expression in the paw tissue and gastric mucosa, but exhibited no effect on COX-1 expression or on COX-1 and COX-2 activities. CK exerted anti-inflammatory and analgesic effects, possibly by reducing the catalytic synthesis of PGE2 via downregulation of COX-2 expression.