Anti-nociceptive and anti-inflammatory effect of imperatorin: evidences for involvement of COX-2, iNOS, NF?B and inflammatory cytokines
Anti-nociceptive and anti-inflammatory effect of imperatorin: evidences for involvement of COX-2, iNOS, NF?B and inflammatory cytokines
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DOI：
10.1080/00207454.2019.1667789
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发表时间：
2019-09-28
影响因子：
2.2
通讯作者：
Bhatti, Rajbir
中科院分区：
文献类型：
--
作者：
Singh, Gurjit;Kaur, Jashanpreet;Bhatti, Rajbir
目的：探讨天然呋喃香豆素、欧前胡素的镇痛作用及诱导型环氧合酶（COX-2）、诱导型一氧化氮合酶（iNOS）、NF？B和细胞因子在观察中的作用。材料与方法：采用醋酸和福尔马林诱导小鼠化学痛觉过敏，探讨其抗伤害性作用。用乙酸模型计算欧前胡素的ED50。分别用P物质和l -精氨酸刺激物/前体刺激，定量测定COX-2、iNOS和NF？免疫组化分析脊髓组织中B的表达。炎性细胞因子TNF-？和il - 1 ?采用LPS激发法和随后的ELISA法分析血清中这些炎症介质。采用卡拉胶致足跖水肿实验，探讨欧前胡素的抗炎作用。结果：在醋酸和福尔马林试验中，欧前胡素治疗能显著降低小鼠的伤害性行为。欧前胡素的ED50为4.53 mg/kg。经P物质和l -精氨酸预处理后，欧前胡素在福尔马林试验中的抗伤害活性显著减弱。免疫组化结果显示脊髓COX-2、iNOS和NF？B的表达。欧前胡素可显著降低LPS诱导的TNF-？和il - 1 ?剂量依赖性。在卡拉胶诱导的足跖水肿试验中，欧前胡素的抗炎作用在240？最小的卡拉胶管理。结论：目前的研究表明，欧前胡素的抗伤害和抗炎作用可能是通过抑制COX-2、iNOS、NF？B活性和循环细胞因子的减少。
Aim: The objective of the current investigation was to explore the analgesic effect of naturally occurring furanocoumarin, imperatorin and the involvement of inducible cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), NF?B and cytokines in the observed effect. Materials and methods: Anti-nociceptive effect was explored by inducing chemical hyperalgesia using acetic acid and formalin in mice. ED50 of imperatorin was calculated in acetic acid model. Modulation of cyclooxygenase and nitric oxide pathway by imperatorin was examined by stimulator/precursor challenge with substance P and L-arginine, respectively and quantification of COX-2, iNOS and NF?B expression by immunohistochemical analysis in spinal tissues. Involvement of inflammatory cytokines TNF-? and IL-1? was investigated using LPS challenge and subsequent ELISA analysis of these inflammatory mediators in serum. Carrageenan inflicted paw edema was employed to explore the anti-inflammatory activity of imperatorin. Results: A significant reduction in the nociceptive behaviour was observed with imperatorin treatment in acetic acid and formalin test. ED50 of imperatorin was found to be 4.53?mg/kg. Pre-treatment with substance P and L-arginine significantly attenuated the anti-nociceptive activity of imperatorin in formalin test. Immunohistochemical findings revealed marked decrease in spinal COX-2, iNOS and NF?B expression. Imperatorin administration significantly reduced LPS induced rise in level of TNF-? and IL-1? dose dependently. In carrageenan-induced paw edema test, maximum possible anti-inflammatory effect of imperatorin was evident after 240?min of carrageenan administration. Conclusion: Current investigation revealed that anti-nociceptive and anti-inflammatory potential of imperatorin is probably mediated through the attenuation of COX-2, iNOS, NF?B activity and reduction in circulatory cytokines.