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

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.

Huangqi Guizhi Wuwu decoction; Lipidomics; Metabolomics; Myelin regeneration; Network pharmacology; Oxaliplatin-induced peripheral neurotoxicity.