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鉴定万寿菊 Cav. 的抗伤害活性中的一些生物活性代谢物和抑制性受体

Identification of some bioactive metabolites and inhibitory receptors in the antinociceptive activity of Tagetes lucida Cav.

机构信息

Neuropharmacology of Natural Products Laboratory, Neuroscience Research Department, National institute of Psychiatry "Ramón de la Fuente", Av. México-Xochimilco 101, Col. Sn Lorenzo Huipulco, 14370 México, D. F., Mexico.

Neuropharmacology of Natural Products Laboratory, Neuroscience Research Department, National institute of Psychiatry "Ramón de la Fuente", Av. México-Xochimilco 101, Col. Sn Lorenzo Huipulco, 14370 México, D. F., Mexico.

出版信息

Life Sci. 2019 Aug 15;231:116523. doi: 10.1016/j.lfs.2019.05.079. Epub 2019 May 30.

DOI:10.1016/j.lfs.2019.05.079
PMID:31152811
Abstract

Tagetes lucida Cav. is an ancient medicinal plant used to treat different ailments involving neurological diseases and pain. However, scientific studies to validate their medicinal properties as analgesic have not been described. The aim of this study was to evaluate the T. lucida antinociceptive response using pain models. Bioactive compounds and a possible mechanism of action were also explored. Dose-response effects of an ethanol crude extract were investigated in the writhing and formalin tests in mice and rats, respectively. The extract was fractionated to isolate active fractions and bioactive compounds (quercetagetin 7‑O‑β‑d‑glucoside and 6,7‑dimethoxycoumarin) using the formalin test. The antinociceptive effects were compared to the reference drugs (tramadol 10 mg/kg, diclofenac 50 mg/kg, and/or ketorolac 1 mg/kg, i.p.). The ethanol extract was explored in the presence of naloxone (3 mg/kg, i.p. a non-selective opioid receptor antagonist) and WAY100635 (0.5 mg/kg, s.c., a selective 5-HT receptor antagonist) to screen their participation as possible inhibitory mechanisms involved in the antinociceptive response of T. lucida. The ethanol crude extract, fractions, and pure compounds caused a significant antinociceptive response resembling the effect of the reference drugs. Both opioid and 5-HT receptors participated in the analgesic -like activity of the extract, which did not produce gastric damage. On the contrary, the gastric damage produced as an adverse effect of the analgesic ketorolac was prevented when combined with the extract. In conclusion, these preliminary data provide evidence and give support to the properties attributed to T. lucida in the traditional medicine to alleviate pain.

摘要

万寿菊是一种古老的药用植物,用于治疗涉及神经疾病和疼痛的各种疾病。然而,尚未有研究科学验证其作为镇痛药的特性。本研究旨在使用疼痛模型评估万寿菊的镇痛作用。还探索了生物活性化合物和可能的作用机制。在小鼠和大鼠的扭体和福尔马林试验中分别研究了乙醇粗提物的剂量反应效应。使用福尔马林试验分离活性部分和生物活性化合物(槲皮素 7-O-β-D-葡萄糖苷和 6,7-二甲氧基香豆素)对提取物进行了分级。将镇痛作用与参考药物(曲马多 10mg/kg、双氯芬酸 50mg/kg 和/或酮咯酸 1mg/kg,ip)进行了比较。在纳洛酮(3mg/kg,ip,一种非选择性阿片受体拮抗剂)和 WAY100635(0.5mg/kg,sc,一种选择性 5-HT 受体拮抗剂)存在的情况下研究了乙醇提取物,以筛选它们作为可能的抑制机制参与了 T. lucida 的镇痛反应。乙醇粗提物、馏分和纯化合物均引起明显的镇痛作用,类似于参考药物的作用。阿片受体和 5-HT 受体均参与了提取物的镇痛样活性,而提取物不会引起胃损伤。相反,当与提取物结合时,可预防镇痛酮咯酸产生的胃损伤的不利影响。总之,这些初步数据为传统医学中归因于万寿菊的缓解疼痛的特性提供了证据和支持。

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