Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain
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. Method...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2022/6010952 |
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| author | Peng Xi Rui Mao Shiyan Wu Lei Liu Ceng Cai Lei Lu Cailin Zhang Yimei Li |
| author_facet | Peng Xi Rui Mao Shiyan Wu Lei Liu Ceng Cai Lei Lu Cailin Zhang Yimei Li |
| author_sort | Peng Xi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d7f790e22276445b812d641b87dabcc5 |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-d7f790e22276445b812d641b87dabcc52025-02-03T06:08:42ZengWileyMediators of Inflammation1466-18612022-01-01202210.1155/2022/6010952Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic PainPeng Xi0Rui Mao1Shiyan Wu2Lei Liu3Ceng Cai4Lei Lu5Cailin Zhang6Yimei Li7Department of PainDepartment of Tumor CenterDepartment of PainDepartment of PainDepartment of Tumor CenterDepartment of PainDepartment of PainDepartment of PainBackground. 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.http://dx.doi.org/10.1155/2022/6010952 |
| spellingShingle | Peng Xi Rui Mao Shiyan Wu Lei Liu Ceng Cai Lei Lu Cailin Zhang Yimei Li Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain Mediators of Inflammation |
| title | Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain |
| title_full | Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain |
| title_fullStr | Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain |
| title_full_unstemmed | Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain |
| title_short | Using Network Pharmacology and Animal Experiment to Investigate the Therapeutic Mechanisms of Polydatin against Vincristine-Induced Neuropathic Pain |
| title_sort | using network pharmacology and animal experiment to investigate the therapeutic mechanisms of polydatin against vincristine induced neuropathic pain |
| url | http://dx.doi.org/10.1155/2022/6010952 |
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