The therapeutic effects of Hexuetongbi formula to combat the oxaliplatin-induced peripheral neuropathy using network pharmacological methods in rat model
Jingyu Feng1,2, Li Yang1, Jiguo Wang1,2, Jing Zhang1,2, Lizhu Lin2,3*
1Department of Oncology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Shenzhen 518133, China
2The First School of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong, China
3Department of Oncology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong, China
Abstract
The objective of this study was to elucidate the mechanism of the Hexuetongbi formula in treating Chemotherapy-induced Peripheral Neuropathy (CIPN) using network pharmacology, pharmacodynamics, and mechanistic approaches in an oxaliplatin-induced peripheral neuropathy rat model. Network pharmacology is crucial for understanding the multi-target effects of the Hexuetongbi formula on CIPN. This approach allows for a comprehensive mapping of the complex interactions between the formula’s constituents and the biological pathways involved in CIPN, revealing potential synergistic effects and enhancing the formula’s pharmacological validation. The Hexue Tongbi formula’s impact was analyzed on rats undergoing peripheral neuropathy, observing changes in the morphology of L4-6 dorsal root ganglion neurons through hematoxylin and eosin (HE) staining. Simultaneously, a network pharmacology approach was employed, utilizing TCMSP and GeneCards databases to identify common targets between CIPN and Hexue Tongbi’s therapeutic entities. These core targets were scrutinized through GO enrichment and KEGG pathway analysis. To validate the findings, mRNA and protein expression levels in the L4-6 dorsal root ganglion were examined using quantitative PCR and Western Blot assays. Significant modifications were observed in the frequency of cold stimulus withdrawal reflexes and the L4-6 dorsal root ganglion neurons, while the mechanical withdrawal reflex threshold displayed a considerable decrease. In rats treated with the Hexuetongbi formula post-oxaliplatin, there was noteworthy mitigation in the cold stimulation paw withdrawal threshold and augmentation in the mechanical stimulation paw withdrawal threshold. Network pharmacology identified 19 active constituents in Hexuetongbi and 35 targets for CIPN, with the PI3K/Akt signaling pathway emerging as a prominent target. There was a significant upregulation in PI3K, Akt1, Akt2, and Bcl-2 compared to controls, suggesting that Hexuetongbi effectively mitigates oxaliplatin-induced peripheral neuropathy through the modulation of the PI3K/Akt and Bcl-2 pathways.
Keywords: Oxaliplatin, Chemotherapy-induced peripheral neuropathy, Traditional Chinese medicine, Dorsal root ganglion, Apoptosis
