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姜黄素在棉球肉芽肿袋模型中增强了环氧化酶抑制剂的抗炎活性。

Curcumin potentiates the anti-inflammatory activity of cyclooxygenase inhibitors in the cotton pellet granuloma pouch model.

作者信息

Nandal Shivender, Dhir Ashish, Kuhad Anurag, Sharma Sameer, Chopra Kanwaljit

机构信息

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

出版信息

Methods Find Exp Clin Pharmacol. 2009 Mar;31(2):89-93. doi: 10.1358/mf.2009.31.2.1357705.

DOI:10.1358/mf.2009.31.2.1357705
PMID:19455263
Abstract

Curcumin is a yellow-colored plant polyphenol with a long history of medicinal use in ayurvedic, Chinese and Japanese medicine. Studies have reported the cyclooxygenase COX-2-inhibitory activity of this polyphenol; however, none of the studies have established its antiinflammatory activity in the rat cotton pellet granuloma pouch model, which mimics subchronic inflammation in humans. The present study was conducted to evaluate the effect of curcumin in the cotton pellet granuloma pouch model. Furthermore, the interaction of curcumin with standard anti-inflammatory drugs at subeffective doses was studied to evaluate its potential role as adjuvant therapy. Administration of curcumin (240 mg/kg i.p.), aspirin (160 mg/kg i.p.) or rofecoxib (5 mg/kg i.p.) for 6 days in the cotton pellet granuloma pouch test exhibited significant anti-inflammatory activity, as demonstrated by a decrease in both dry and wet weights of the cotton pellet as compared to the control animals. Lower doses of curcumin (120 mg/kg i.p.), aspirin (80 mg/kg i.p.) or rofecoxib (2.5 mg/kg i.p.) were ineffective. However, the combination of a subeffective dose of curcumin (120 mg/kg i.p.) with submaximal doses of aspirin (80 mg/kg i.p.) or rofecoxib (2.5 mg/kg i.p.) produced a synergistic effect. Furthermore, there was marked increase in tumor necrosis factor-alpha (TNF-alpha) levels (estimated by enzyme-linked immunosorbent assay, ELISA) in the serum of the animals implanted with cotton pellets presenting marked inflammatory events. Daily administration of curcumin, aspirin or rofecoxib decreased the levels of TNF-alpha, further demonstrating anti-inflammatory activity. Curcumin in combination with aspirin or rofecoxib caused a further decrease in serum TNF-alpha levels. In conclusion, the results of the present study demonstrate an anti-inflammatory effect for curcumin in the cotton pellet granuloma pouch test, possibly acting through COX enzyme inhibition, and further inhibiting the generation of inflammatory mediators such as TNF-alpha. These results point toward the usefulness of curcumin as adjuvant drug therapy along with standard anti-inflammatory drugs.

摘要

姜黄素是一种黄色植物多酚,在阿育吠陀医学、中医和日本医学中有着悠久的药用历史。研究报道了这种多酚的环氧化酶COX - 2抑制活性;然而,尚无研究在模拟人类亚慢性炎症的大鼠棉球肉芽肿袋模型中证实其抗炎活性。本研究旨在评估姜黄素在棉球肉芽肿袋模型中的作用。此外,还研究了姜黄素与亚有效剂量的标准抗炎药物的相互作用,以评估其作为辅助治疗的潜在作用。在棉球肉芽肿袋试验中,腹腔注射姜黄素(240 mg/kg)、阿司匹林(160 mg/kg)或罗非昔布(5 mg/kg)6天,均表现出显著的抗炎活性,与对照动物相比,棉球的干重和湿重均有所降低。较低剂量的姜黄素(腹腔注射120 mg/kg)、阿司匹林(腹腔注射80 mg/kg)或罗非昔布(腹腔注射2.5 mg/kg)无效。然而,亚有效剂量的姜黄素(腹腔注射120 mg/kg)与次最大剂量的阿司匹林(腹腔注射80 mg/kg)或罗非昔布(腹腔注射2.5 mg/kg)联合使用产生了协同作用。此外,在植入棉球且出现明显炎症反应的动物血清中,肿瘤坏死因子-α(TNF-α)水平(通过酶联免疫吸附测定法,ELISA测定)显著升高。每日给予姜黄素、阿司匹林或罗非昔布可降低TNF-α水平,进一步证明了其抗炎活性。姜黄素与阿司匹林或罗非昔布联合使用可使血清TNF-α水平进一步降低。总之,本研究结果表明姜黄素在棉球肉芽肿袋试验中具有抗炎作用,可能是通过抑制COX酶,并进一步抑制TNF-α等炎症介质的产生。这些结果表明姜黄素作为标准抗炎药物的辅助药物治疗具有应用价值。

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