Xiongshao Zhitong granules alleviate nitroglycerin-induced migraine by regulating the TRPV1-mediated NLRP3 inflammatory pathway in rats

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-11 DOI:10.1016/j.phymed.2025.156754

Yuxi Wang , Song Yang , Xiaoyao Liu , Cong Chen , Qian Li , Xiaozhu Wang , Wenhui Xu , Jian Gao , Yao Wang , Weiling Wang , Ting Wang

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Abstract

Background

Migraine is a prevalent neurological disorder accompanied by a considerable economic burden. Xiongshao Zhitong granules (XSZT) have anti-inflammatory and analgesic functions in the clinic and are used for migraine therapy. However, the mechanisms by which XSZT treats migraine remain unclear.

Purpose

To discover the underlying mechanism and active ingredients of XSZT in the treatment of migraine.

Methods

The nitroglycerin (NTG)-induced chronic migraine (CM) model was established and used to detect the therapeutic effect of XSZT on migraine. To elucidate the mechanism, we detected transient receptor potential vanilloid 1 (TRPV1) -mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation in the CM rat model and the LPS-induced inflammatory BV-2 cell model using Western blotting, immunofluorescence and ELISA techniques. The potentially active ingredients of XSZT were determined by UHPLC-LTQ-Orbitrap MS, molecular docking, and surface plasmon resonance.

Results

Our findings revealed that XSZT reduced the number of head scratching, increased the periorbital pain threshold and shortened the time spent in the dark box, decreased c-Fos expression in the CM rat model, suggesting an analgesic effect of XSZT on migraine. XSZT inhibited neurogenic inflammation, including downregulating CGRP, TNF-α, IL-1β and IL-18 levels and decreasing the degranulation rate of mast cells. Additionally, XSZT suppressed the expression and activation of TRPV1 and the NLRP3 inflammasome in the trigeminal nucleus caudalis. In vitro experiments confirmed that activated TRPV1 increased the level of the NLRP3 inflammasome by increasing intracellular calcium levels. Galloylpaeoniflorin, isogastrin, ellagic acid and salvianolic acid A interacted with TRPV1 and inhibited IL-1β secretion.

Conclusion

XSZT plays a therapeutic role in migraine through regulating TRPV1-mediated NLRP3 inflammatory activation and galloylpaeoniflorin, isogastrin, ellagic acid and salvianolic acid A might be the active ingredients of XSZT, which provides an experimental basis for the clinical treatment of migraine.

Abstract Image

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雄芍止痛颗粒通过调节trpv1介导的NLRP3炎症通路减轻硝酸甘油所致大鼠偏头痛

背景偏头痛是一种常见的神经系统疾病，伴随着相当大的经济负担。雄芍智通颗粒（XSZT）在临床上具有抗炎和镇痛作用，被用于偏头痛的治疗。方法建立硝酸甘油（NTG）诱导的慢性偏头痛（CM）模型，用于检测 XSZT 对偏头痛的治疗效果。为阐明其作用机制，我们采用Western印迹、免疫荧光和ELISA技术检测了在CM大鼠模型和LPS诱导的炎性BV-2细胞模型中瞬时受体电位类香草素1（TRPV1）介导的NOD样受体蛋白3（NLRP3）炎性体激活。结果我们的研究结果表明，XSZT能减少CM大鼠模型的搔头次数、提高眶周疼痛阈值并缩短在暗箱中的时间、降低c-Fos的表达，这表明XSZT对偏头痛有镇痛作用。XSZT 可抑制神经源性炎症，包括下调 CGRP、TNF-α、IL-1β 和 IL-18 的水平，降低肥大细胞的脱颗粒率。此外，XSZT 还能抑制三叉神经尾核中 TRPV1 和 NLRP3 炎性体的表达和活化。体外实验证实，激活的 TRPV1 通过增加细胞内的钙水平来提高 NLRP3 炎症体的水平。结论XSZT通过调节TRPV1介导的NLRP3炎症激活对偏头痛有治疗作用，五倍子芍药苷、异胃泌素、鞣花酸和丹酚酸A可能是XSZT的活性成分，这为偏头痛的临床治疗提供了实验依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.