Department of Biochemistry, Kerala University, Trivandrum, India.
Inflamm Res. 2013 Apr;62(4):367-76. doi: 10.1007/s00011-013-0588-1. Epub 2013 Jan 24.
The present study evaluates the anti-inflammatory effect of the quinoline alkaloid skimmianine (SKM), isolated from Ruta graveolens L., against carrageenan-induced acute inflammation.
SKM at a dose of 5.0 mg/kg body weight was found to be the minimal concentration for maximal edema inhibition. Carrageenan suspension was administered into the sub-plantar tissue of the right hind paw 1 h after SKM and diclofenac (20 mg/kg) administration (i.p.). Paw edema was determined 3 h after carrageenan administration. The rats were then killed and mRNA expressions of TNF-α and IL-6, levels of PGE2 and TBARS, activities of COX-2, 5-LOX, SOD, catalase, glutathione peroxidase (GPx) and myeloperoxidase (MPO) and the level of nitrite were measured.
SKM treatment resulted in a decrease in the mRNA levels of TNF-α and IL-6, which are upstream events of the inflammatory cascade. The levels of PGE2 and NO and the activities of COX-2 and 5-LOX were also significantly reduced after SKM treatment. Neutrophil infiltration, lipid peroxidation and associated oxidative stress in the paw tissue were reduced following SKM treatment.
These results support the anti-inflammatory properties of skimmianine and its multi-targeted mechanism of action, suggesting its potential therapeutic efficacy in various inflammatory diseases.
本研究评估了瑞香狼毒中分离得到的喹啉生物碱斯米宁(SKM)对卡拉胶诱导的急性炎症的抗炎作用。
SKM 的剂量为 5.0mg/kg 体重,被发现是抑制水肿的最大浓度。在 SKM 和双氯芬酸钠(20mg/kg)给药(ip)1 小时后,将卡拉胶混悬液注入右后爪的足底组织。在卡拉胶给药后 3 小时测定爪水肿。然后处死大鼠,测量 TNF-α 和 IL-6 的 mRNA 表达水平、PGE2 和 TBARS 水平、COX-2、5-LOX、SOD、过氧化氢酶、谷胱甘肽过氧化物酶(GPx)和髓过氧化物酶(MPO)的活性以及亚硝酸盐的水平。
SKM 治疗导致 TNF-α 和 IL-6 的 mRNA 水平降低,这是炎症级联的上游事件。SKM 治疗后,PGE2 和 NO 的水平以及 COX-2 和 5-LOX 的活性也显著降低。SKM 治疗后,爪组织中的中性粒细胞浸润、脂质过氧化和相关的氧化应激减少。
这些结果支持斯米宁的抗炎特性及其多靶点作用机制,表明其在各种炎症性疾病中的潜在治疗效果。