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甘草素通过激活 BK 通道和降低 NO 水平减轻啮齿动物的炎症和痛觉过敏。

Glabridin Alleviates Inflammation and Nociception in Rodents by Activating BK Channels and Reducing NO Levels.

机构信息

Department of Pharmacology, Faculty of Medicine, University of Adiyaman.

Department of Pharmacology, Faculty of Medicine, University of Ankara Yildirim Beyazit.

出版信息

Biol Pharm Bull. 2020 May 1;43(5):884-897. doi: 10.1248/bpb.b20-00038. Epub 2020 Mar 6.

DOI:10.1248/bpb.b20-00038
PMID:32147624
Abstract

Inflammation, and the pain that accompanies it, is a natural response of the body. The licorice plant (Glycyrrhiza glabra) have demonstrated anti-inflammatory, anti-edematous, and anti-nociceptive effects of its extracts. The effective ingredient remains unidentified; however, one possibility is the unique isoflavone glabridin. The anti-nociceptive, and anti-inflammatory effects of glabridin and its possible mechanism with focus on the large conductance Ca-activated K (BK) channels and L-arginine-nitric oxide (NO) pathway were examined by using different tests. In order to determine the anti-edematous, anti-nociceptive, and anti-oxidative effects of glabradin, some tests such as the tail flick, hotplate, carrageenan-induced paw edema, air pouch, acetic-acid-induced writhing, formalin, and capsaicin tests, as well as toxicity and open field tests were made. Glabridin was administered to rats (n = 8) or mice (n = 8) for 3 d at 3 doses (10, 20, and 40 mg/kg). Glabridin inhibited cytokine production and showed an anti-nociceptive response via the activating of BK channels and downregulating NO level and partially transient receptor potential vanilloid-1 pathways. It also demonstrated anti-inflammatory effects by inhibiting cyclooxygenase (COX) activity, while showing no cytotoxicity. Glabridin, however, showed no anti-nociceptive effect in the neurogenic phase. Glabridin is a promising substance in terms of its anti-nociceptive and anti-inflammatory effects by disrupting peripheral NO production, inhibiting cyclic guanosine monophosphate (cGMP) activation and activating BK channels and its lack of acute and subacute toxic effects.

摘要

炎症及其伴随的疼痛是身体的自然反应。甘草植物(Glycyrrhiza glabra)的提取物具有抗炎、抗水肿和抗伤害感受的作用。有效成分尚未确定;然而,一种可能性是独特的异黄酮甘草素。使用不同的测试方法研究了甘草素的抗伤害感受和抗炎作用及其可能的机制,重点是大电导钙激活钾(BK)通道和 L-精氨酸-一氧化氮(NO)途径。为了确定甘草素的抗水肿、抗伤害感受和抗氧化作用,进行了一些测试,如尾巴拍打、热板、角叉菜胶诱导的爪水肿、气囊、醋酸诱导的扭曲、甲醛和辣椒素测试,以及毒性和旷场测试。甘草素在 3 天内以 3 个剂量(10、20 和 40mg/kg)施用于大鼠(n=8)或小鼠(n=8)。甘草素通过激活 BK 通道和下调 NO 水平以及部分瞬时受体电位香草素-1 途径抑制细胞因子产生并表现出抗伤害感受反应。它还通过抑制环加氧酶(COX)活性表现出抗炎作用,同时没有细胞毒性。然而,甘草素在神经原性阶段没有表现出抗伤害感受作用。甘草素通过破坏外周 NO 产生、抑制环鸟苷单磷酸(cGMP)激活和激活 BK 通道,以及缺乏急性和亚急性毒性作用,在抗伤害感受和抗炎作用方面具有广阔的应用前景。

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