Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2
Abstract Introduction We tried to show the effect of sinomenine (SIN) in diabetic peripheral neuropathic pain (DPNP) and the related underlying mechanism. Methods Network pharmacological analysis and bioinformatics analysis were carried out for identification of the active ingredients of Sinomenium...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-03-01
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| Series: | Journal of Diabetes Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jdi.13938 |
| _version_ | 1797895052786139136 |
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| author | Ji Chen Peng Guo Xinxin Liu Huizhi Liao Kemin Chen Yuxia Wang Jie Qin Fengrui Yang |
| author_facet | Ji Chen Peng Guo Xinxin Liu Huizhi Liao Kemin Chen Yuxia Wang Jie Qin Fengrui Yang |
| author_sort | Ji Chen |
| collection | DOAJ |
| description | Abstract Introduction We tried to show the effect of sinomenine (SIN) in diabetic peripheral neuropathic pain (DPNP) and the related underlying mechanism. Methods Network pharmacological analysis and bioinformatics analysis were carried out for identification of the active ingredients of Sinomenium acutum and the related genes. The DPNP rat model was constructed and primary rat spinal cord microglial cells were isolated for in vitro cell experiments. The therapeutic role of SIN in DPNP was determined in vivo and in vitro through analysis of microglial cell activation and inflammatory response. Results Therapeutic role of S. acutum in DPNP was mainly achieved by regulating 14 key genes, among which the target gene prostaglandin‐endoperoxide synthase 2 (PTGS2) of SIN might be the key gene. An in vivo experiment showed that SIN inactivated the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating PTGS2, which relieved pain symptoms in DPNP rats. It was confirmed in vivo that SIN inhibited the pathway through PTGS2 to alleviate the activation of spinal cord microglial cells and inflammatory response. Conclusion SIN decreases the expression of PTGS2 to inactivate the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 signaling pathway, which inhibits microglial activation, as well as the release of inflammatory factors, thus alleviating DPNP. |
| first_indexed | 2024-04-10T07:20:19Z |
| format | Article |
| id | doaj.art-09bc17f3c4fa4683bf159d8c5fc9fa80 |
| institution | Directory Open Access Journal |
| issn | 2040-1116 2040-1124 |
| language | English |
| last_indexed | 2024-04-10T07:20:19Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj.art-09bc17f3c4fa4683bf159d8c5fc9fa802023-02-24T12:37:44ZengWileyJournal of Diabetes Investigation2040-11162040-11242023-03-0114336437510.1111/jdi.13938Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2Ji Chen0Peng Guo1Xinxin Liu2Huizhi Liao3Kemin Chen4Yuxia Wang5Jie Qin6Fengrui Yang7Department of Endocrinology The First People's Hospital of Huaihua Huaihua ChinaDepartment of Anesthesiology The First People's Hospital of Huaihua Huaihua ChinaDepartment of Anesthesiology The First People's Hospital of Huaihua Huaihua ChinaDepartment of Anesthesiology The First People's Hospital of Huaihua Huaihua ChinaDepartment of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital University of South China Hengyang ChinaDepartment of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital University of South China Hengyang ChinaDepartment of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital University of South China Hengyang ChinaDepartment of Anesthesiology The First People's Hospital of Huaihua Huaihua ChinaAbstract Introduction We tried to show the effect of sinomenine (SIN) in diabetic peripheral neuropathic pain (DPNP) and the related underlying mechanism. Methods Network pharmacological analysis and bioinformatics analysis were carried out for identification of the active ingredients of Sinomenium acutum and the related genes. The DPNP rat model was constructed and primary rat spinal cord microglial cells were isolated for in vitro cell experiments. The therapeutic role of SIN in DPNP was determined in vivo and in vitro through analysis of microglial cell activation and inflammatory response. Results Therapeutic role of S. acutum in DPNP was mainly achieved by regulating 14 key genes, among which the target gene prostaglandin‐endoperoxide synthase 2 (PTGS2) of SIN might be the key gene. An in vivo experiment showed that SIN inactivated the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating PTGS2, which relieved pain symptoms in DPNP rats. It was confirmed in vivo that SIN inhibited the pathway through PTGS2 to alleviate the activation of spinal cord microglial cells and inflammatory response. Conclusion SIN decreases the expression of PTGS2 to inactivate the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 signaling pathway, which inhibits microglial activation, as well as the release of inflammatory factors, thus alleviating DPNP.https://doi.org/10.1111/jdi.13938Diabetic peripheral neuropathic painSinomenineSpinal cord microglia |
| spellingShingle | Ji Chen Peng Guo Xinxin Liu Huizhi Liao Kemin Chen Yuxia Wang Jie Qin Fengrui Yang Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2 Journal of Diabetes Investigation Diabetic peripheral neuropathic pain Sinomenine Spinal cord microglia |
| title | Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2 |
| title_full | Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2 |
| title_fullStr | Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2 |
| title_full_unstemmed | Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2 |
| title_short | Sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating prostaglandin‐endoperoxide synthase 2 |
| title_sort | sinomenine alleviates diabetic peripheral neuropathic pain through inhibition of the inositol requiring enzyme 1 alpha x box binding protein 1 pathway by downregulating prostaglandin endoperoxide synthase 2 |
| topic | Diabetic peripheral neuropathic pain Sinomenine Spinal cord microglia |
| url | https://doi.org/10.1111/jdi.13938 |
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