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Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain

Authors :
Peng Xi
Rui Mao
Shiyan Wu
Lei Liu
Ceng Cai
Lei Lu
Cailin Zhang
Yimei Li
Source :
Mediators of Inflammation. 2022:1-13
Publication Year :
2022
Publisher :
Hindawi Limited, 2022.

Abstract

Background. Polydatin (PD) is the primary active compound in Polygonum cuspidatum Sieb and has been demonstrated to exert anti-inflammatory and neuroprotective activities. In the present study, we aimed to explore the therapeutic mechanisms of PD against chemotherapy-induced neuropathic pain. Methods. The putative targets of PD were obtained from the CTD and SwissTargetPrediction databases. Neuropathic pain- and VIN-related targets were collected from the CTD and GeneCards databases. Subsequently, the intersection targets were obtained using the Venn tool, and the protein-protein interaction (PPI) was constructed by the STRING database. GO and KEGG enrichment analyses were performed to investigate the biological functions of the intersection targets. Further, a rat model of VIN-induced neuropathic pain was established to confirm the reliability of the network pharmacology findings. Results. A total of 46 intersection targets were identified as potential therapeutic targets, mainly related to neuroinflammation. KEGG pathway analysis indicated that the IL-17 signaling pathway was involved in the mechanism of the antinociceptive effect of PD. PPI network analysis indicated that RELA, IL-6, TP53, MAPK3, and MAPK1 were located at crucial nodes in the network. Additionally, PD exerted an antinociceptive effect by increasing the nociceptive threshold. The results of qRT-PCR, western blot, and immunohisochemistry indicated that PD inhibited the IL-6, TP53, and MAPK1 levels in VIN-induced neuropathic pain rats. Conclusions. Overall, this research provided evidence that suppressing inflammatory signaling pathways might be a potential mechanism action of PD’s antinociceptive effect against VIN-induced neuropathic pain.

Details

ISSN :
14661861 and 09629351
Volume :
2022
Database :
OpenAIRE
Journal :
Mediators of Inflammation
Accession number :
edsair.doi.dedup.....bd57e5d84f035d027d3d3350acbebf4b