Isoliquiritigenin alleviates abnormal sarcomere contraction and inflammation in myofascial trigger points via the IL‐17RA/Act1/p38 pathway in rats

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-25 DOI:10.1016/j.phymed.2025.156993

Xuan Li , Tian Qi , Lingwei Zhou , Pengyu Lin , Qinghe Chen , Xiaoyue Li , Ren He , Shaozhong Yang , Yu Liu , Feng Qi

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Abstract

Background

Myofascial trigger points (MTrPs) are a primary cause of myofascial pain syndrome. Current studies suggest that MTrPs consist of persistent sarcomere contraction and an inflammatory microenvironment. IL-17 has been implicated in the progression of inflammation. However, its expression of IL-17 in MTrPs and the underlying mechanisms remain unclear.

Purpose

This study aimed to characterise IL-17 signalling and elucidate the associated molecular mechanisms in the context of MTrPs, and evaluate the therapeutic effects of isoliquiritigenin (ISL) on MTrPs.

Methods

We examined IL-17A signalling expression using immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis in MTrPs rat. Haematoxylin and eosin staining and transmission electron microscopy were used to assess muscle fibre and sarcomere morphology. The Randall-Selitto test was employed to evaluate pain-like behaviours in rats. Dihydroethidium staining, JC-1 assay, and ATP quantification were used to assess inflammation-associated mitochondrial function in vitro and in vivo. Additionally, molecular docking, cellular thermal shift, and drug affinity responsive target stability assays were conducted to examine the interaction between ISL and the IL-17 receptor subunit A (IL‐17RA) protein.

Results

IL-17A and IL-17RA were significantly expressed in rats with MTrPs. These rats exhibited elevated oxidative stress level and reduced ATP production. Studies on IL-17A stimulated myotubes and gastrocnemius muscle indicated that IL-17RA signalling contributes to inflammation, abnormal sarcomere contraction and mitochondrial dysfunction in MTrPs. Lentivirus-mediated IL-17RA knockdown in the rats further confirmed these findings. Inhibition of the mitogen-activated protein kinase p38 and subsequent rescue experiments highlighted the critical role of IL-17RA/Act1/p38 signalling. Notably, molecular docking and validation experiments revealed that ISL binds to and inhibits IL-17RA, thereby disrupting IL-17RA/Act1/p38 signalling, and ultimately suppressing the maintenance of MTrPs.

Conclusion

This study demonstrates that ISL ameliorates sarcomere contraction and inflammatory responses by inhibiting the IL-17RA/Act1/p38 signalling pathway in rats with MTrPs, highlighting its potential as a novel therapeutic strategy for myofascial pain syndrome (MPS).

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异尿素通过IL - 17RA/Act1/p38通路减轻大鼠异常肌瘤收缩和肌筋膜触发点炎症

背景：肌筋膜触发点（MTrPs）是肌筋膜疼痛综合征的主要原因。目前的研究表明MTrPs由持续的肌瘤收缩和炎症微环境组成。IL-17与炎症的进展有关。然而，IL-17在MTrPs中的表达及其潜在机制尚不清楚。目的研究IL-17在MTrPs中的信号转导及相关分子机制，并评价ISL对MTrPs的治疗作用。方法采用免疫组织化学、逆转录-定量聚合酶链反应和western blot检测MTrPs大鼠IL-17A信号表达。采用苏木精和伊红染色及透射电镜观察肌纤维和肌节形态。采用Randall-Selitto试验评价大鼠的类痛行为。使用双氢乙啶染色、JC-1测定和ATP定量来评估炎症相关的线粒体功能在体外和体内。此外，我们还进行了分子对接、细胞热位移和药物亲和力响应靶稳定性分析，以研究ISL与IL-17受体亚基A （IL‐17RA）蛋白之间的相互作用。结果il - 17a和IL-17RA在MTrPs大鼠中有显著表达。这些大鼠表现出氧化应激水平升高和ATP产生减少。对IL-17A刺激的肌管和腓肠肌的研究表明，IL-17RA信号传导有助于MTrPs的炎症、异常肌节收缩和线粒体功能障碍。慢病毒介导的大鼠IL-17RA敲低进一步证实了这些发现。丝裂原活化蛋白激酶p38的抑制和随后的救援实验强调了IL-17RA/Act1/p38信号传导的关键作用。值得注意的是，分子对接和验证实验表明，ISL结合并抑制IL-17RA，从而破坏IL-17RA/Act1/p38信号传导，最终抑制MTrPs的维持。结论本研究表明，ISL通过抑制IL-17RA/Act1/p38信号通路，改善MTrPs大鼠的肌节收缩和炎症反应，突出了其作为肌筋膜疼痛综合征（MPS）治疗新策略的潜力。

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.