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通过瞬时受体电位香草酸亚型1调节减轻大鼠模型中辣椒素诱导的机械性异常性疼痛。

alleviated capsaicin-induced mechanical allodynia in a rat model through transient receptor potential vanilloid 1 modulation.

作者信息

Jaffal Sahar Majdi, Al-Najjar Belal Omar, Abbas Manal Ahmad

机构信息

Department of Biological Sciences, Faculty of Science, The University of Jordan, Amman, Jordan.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.

出版信息

Korean J Pain. 2021 Jul 1;34(3):262-270. doi: 10.3344/kjp.2021.34.3.262.

Abstract

BACKGROUND

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel implicated in pain sensation in response to heat, protons, and capsaicin (CAPS). It is well established that TRPV1 is involved in mechanical allodynia. This study investigates the effect of (Fabaceae) in CAPS-induced mechanical allodynia and its mechanism of action.

METHODS

Mechanical allodynia was induced by the intraplantar (ipl) injection of 40 μg CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 μg methanolic leaf extract or 2.5% diclofenac sodium 20 minutes before CAPS injection. Paw withdrawal threshold (PWT) was measured using von Frey filament 30, 90, and 150 minutes after CAPS injection. A molecular docking tool, AutoDock 4.2, was used to study the binding energies and intermolecular interactions between constituents and TRPV1 receptor.

RESULTS

The ipsilateral ipl injection of before CAPS injection increased PWT in rats at all time points. decreased mechanical allodynia by 5.35-fold compared to a 3.59-fold decrease produced by diclofenac sodium. The ipsilateral pretreatment with TRPV1 antagonist (300 μg 4-[3-Chloro-2-pyridinyl]- N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 μg butoxamine) attenuated the action of . Depending on molecular docking results, the activity of the extract could be attributed to the bindings of campesterol, stigmasterol, and ononin compounds to TRPV1.

CONCLUSIONS

alleviated CAPS-induced mechanical allodynia through 2 mechanisms: the direct modulation of TRPV1 and the involvement of β2 adrenoreceptor signaling.

摘要

背景

瞬时受体电位香草酸亚型1(TRPV1)是一种非选择性阳离子通道,与热、质子和辣椒素(CAPS)引起的疼痛感觉有关。TRPV1参与机械性异常性疼痛已得到充分证实。本研究调查了[植物名称,豆科]在CAPS诱导的机械性异常性疼痛中的作用及其作用机制。

方法

通过向雄性Wistar大鼠左后爪足底注射40μg CAPS诱导机械性异常性疼痛。在注射CAPS前20分钟,动物接受100μg[植物名称]甲醇叶提取物或2.5%双氯芬酸钠的足底注射。在注射CAPS后30、90和150分钟,使用von Frey细丝测量爪退缩阈值(PWT)。使用分子对接工具AutoDock 4.2研究[植物名称]成分与TRPV1受体之间的结合能和分子间相互作用。

结果

在注射CAPS前同侧足底注射[植物名称]可使大鼠在所有时间点的PWT增加。与双氯芬酸钠产生的3.59倍降低相比,[植物名称]使机械性异常性疼痛降低了5.35倍。用TRPV1拮抗剂(300μg 4-[3-氯-2-吡啶基]-N-[4-[1,1-二甲基乙基]苯基]-1-哌嗪甲酰胺[BCTC])以及β2-肾上腺素能受体拮抗剂(150μg布托沙明)进行同侧预处理可减弱[植物名称]的作用。根据分子对接结果,提取物的活性可归因于菜油甾醇、豆甾醇和鹰嘴豆芽素化合物与TRPV1的结合。

结论

[植物名称]通过两种机制减轻CAPS诱导的机械性异常性疼痛:直接调节TRPV1和β2肾上腺素能受体信号传导的参与。

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