Huangqi Guizhi Wuwu decoction alleviate Oxaliplatin-Induced Peripheral Neuropathy by adjusting the myelin regeneration

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-01 DOI:10.1016/j.phymed.2025.157039

Xueying Yang , Huaying Zhu , Zhiyu Li , Qianyu Wang , Yingjie Gao , Ziwen Li , Lihuiping Tao , Liu Li , Dongdong Sun , Lin Zhang , Weixing Shen , Haibo Cheng

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引用次数: 0

Abstract

Objective

This study aimed to investigate the effect and underlying mechanism of Huangqi Guizhi Wuwu decoction (HQGZWWD) in preventing Oxaliplatin-induced peripheral neurotoxicity (OIPN) in rat models.

Methods

Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) was utilized for comprehensive characterization of HQGZWWD phytochemicals and their biodistribution in plasma and dorsal root ganglion (DRG) tissues. An established OIPN rodent model was generated through intraperitoneal administration of oxaliplatin, with therapeutic outcomes assessed via behavioral assessments and histopathological evaluations. Subsequent multi-omics investigations incorporated untargeted metabolomic profiling and network pharmacology prediction. A multimodal validation approach encompassing myelin structural analysis, immunofluorescence, ELISA, lipidomics and Western blot was systematically implemented.

Results

Comprehensive phytochemical profiling identified 66 bioactive constituents in HQGZWWD, with quantifiable plasma concentrations detected for 4 compounds and 5 compounds demonstrating significant DRG tissue penetration. The preventive effects of OIPN were validated through both in vitro and in vivo experiments. Metabolomics analysis identified 14 differential metabolites, which were enriched in taurine, hypotaurine, and beta-alanine metabolism. Network pharmacology analysis and Western blot suggested that HQGZWWD exerted its effects through Neuroactive ligand-receptor interaction pathway. Myelin staining and G ratio measurement demonstrated dose-dependent myelin regeneration following HQGZWWD intervention. Western blot demonstrated dose-dependent upregulation of myelin specific proteins MPZ and PMP22 by HQGZWWD. Immunofluorescence, ELISA and Western blot revealed inhibited microglial activation and downregulation of IL-1 and MCP-1. Lipidomics identified 11 differentially expressed lipids, predominantly phospholipids. Finally, by constructing a phospholipase enzyme spectrum, the changes in lipidomics induced by HQGZWWD were further validated.

Conclusion

HQGZWWD prevents and treats OIPN by regulating myelin regeneration.

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黄芪桂枝五物汤通过调节髓鞘再生减轻奥沙利铂所致周围神经病变

目的探讨黄芪桂枝五物汤（HQGZWWD）对奥沙利铂所致大鼠周围神经毒性（OIPN）的预防作用及其机制。方法采用超高效液相色谱-质谱法（UPLC-MS）综合表征HQGZWWD植物化学物质及其在血浆和背根神经节（DRG）组织中的生物分布。通过腹腔注射奥沙利铂建立OIPN啮齿动物模型，通过行为评估和组织病理学评估治疗效果。随后的多组学研究包括非靶向代谢组学分析和网络药理学预测。系统地实施了髓磷脂结构分析、免疫荧光、ELISA、脂质组学和Western blot等多模式验证方法。结果经综合植物化学分析，鉴定出66种活性成分，其中4种化合物可定量血药浓度，5种化合物具有显著的DRG组织穿透性。通过体外和体内实验验证了OIPN的预防作用。代谢组学分析鉴定出14种差异代谢物，这些代谢物富含牛磺酸、次牛磺酸和β -丙氨酸代谢。网络药理学分析和Western blot分析表明，HQGZWWD通过神经活性配体-受体相互作用途径发挥作用。髓磷脂染色和G比值测定显示HQGZWWD干预后髓磷脂再生呈剂量依赖性。Western blot显示HQGZWWD对髓磷脂特异性蛋白MPZ和PMP22的剂量依赖性上调。免疫荧光、ELISA和Western blot结果显示，IL-1和MCP-1的激活和下调均受到抑制。脂质组学鉴定出11种差异表达的脂质，主要是磷脂。最后，通过构建磷脂酶谱，进一步验证HQGZWWD诱导的脂质组学变化。结论hqgzwwd通过调节髓鞘再生来预防和治疗OIPN。

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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.