Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Meishan Road 81, Hefei, 230032, China.
Inflammopharmacology. 2019 Feb;27(1):157-166. doi: 10.1007/s10787-018-0504-y. Epub 2018 Jun 26.
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, 10, 10, 10, 10 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 224 mg/kg alleviated xylene-induced ear oedema, whereas CK at 40, 80, and 160 mg/kg alleviated carrageenan-induced paw oedema. CK at 224 mg/kg showed an analgesic effect against acetic acid-induced pain. CK at 40, 80, and 160 mg/kg significantly increased rat inflammatory pain threshold, but had no effect on heat-induced pain threshold. CK at 10, 20, 40, 80, and 160 mg/kg reduced PGE2 level in the paw tissue, but showed no effect on that in the gastric mucosa. CK at 20, 40, 80, and 160 mg/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.
本研究旨在评估人参皂苷代谢产物化合物 K（CK）的抗炎和镇痛活性及其机制。
采用二甲苯诱导的小鼠耳肿胀模型和角叉菜胶诱导的大鼠足肿胀模型评价 CK 对急性炎症的影响。采用热刺激、醋酸和角叉菜胶诱导的痛觉超敏评价 CK 的镇痛作用。采用酶联免疫吸附试验（ELISA）检测角叉菜胶诱导的大鼠足肿胀和胃黏膜中前列腺素 E2（PGE2）、环氧化酶-1（COX-1）和 COX-2 的水平。采用 Western blot 检测角叉菜胶诱导的大鼠足肿胀和胃黏膜中 COX-1 和 COX-2 的表达。通过测量大鼠腹腔巨噬细胞中 6-酮-PGF1α和 PGE2 的产生来评价 CK（10、10、10、10、10 μM）对 COX-1 和 COX-2 活性的体外作用。
7、14、28、56、112 和 224 mg/kg 的 CK 减轻二甲苯诱导的耳肿胀，而 40、80 和 160 mg/kg 的 CK 减轻角叉菜胶诱导的足肿胀。224 mg/kg 的 CK 对醋酸诱导的疼痛具有镇痛作用。40、80 和 160 mg/kg 的 CK 显著增加大鼠炎症性疼痛阈值，但对热诱导的疼痛阈值没有影响。10、20、40、80 和 160 mg/kg 的 CK 降低足组织中的 PGE2 水平，但对胃黏膜中的 PGE2 水平没有影响。20、40、80 和 160 mg/kg 的 CK 降低足组织和胃黏膜中的 COX-2 表达，但对 COX-1 表达或 COX-1 和 COX-2 活性没有影响。
CK 发挥抗炎和镇痛作用，可能通过下调 COX-2 表达减少 PGE2 的催化合成。
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