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

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.

• Authors: Peng Xi, Rui Mao, Shiyan Wu, Lei Liu, Ceng Cai, Lei Lu, Cailin Zhang, Yimei Li
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2022 Pg. 6010952 ( 2022) ISSN: 1466-1861 [Electronic] United States
• PMID: 36281234 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Peng Xi et al.

Chemical References

• Vincristine
• polydatin
• Interleukin-6
• Interleukin-17
• Drugs, Chinese Herbal
• Anti-Inflammatory Agents
• Antineoplastic Agents
• Analgesics

Topics

• Rats
• Animals
• Vincristine
• Animal Experimentation
• Interleukin-6 (metabolism)
• Interleukin-17
• Network Pharmacology
• Reproducibility of Results
• Neuralgia (chemically induced, drug therapy)
• Drugs, Chinese Herbal (pharmacology)
• Anti-Inflammatory Agents
• Antineoplastic Agents
• Analgesics