Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification
文献类型：期刊论文
| 作者 | Li, Rui; Lou, Qi; Ji, Tingting5; Li, Yincan6; Yang, Haoran ; Ma, Zheng; Zhu, Yu2; Qian, Can2; Yang, Wulin4; Wang, Yijun3
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| 刊名 | JOURNAL OF ETHNOPHARMACOLOGY
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| 出版日期 | 2024-07-15 |
| 卷号 | 329 |
| 关键词 | Astragalus mongholicus Bunge Network pharmacology Cerebral ischemia-reperfusion injury GEO database Molecular docking |
| ISSN号 | 0378-8741 |
| DOI | 10.1016/j.jep.2024.118157 |
| 通讯作者 | Yang, Wulin(yangw@cmpt.ac.cn) ; Wang, Yijun(yijun@ahau.edu.cn) ; Luo, Shengyong(lsy770728@126.com) |
| 英文摘要 | Ethnopharmacological relevance: Astragalus mongholicus Bunge (AMB) is a herb with wide application in traditional Chinese medicine, exerting a wealth of pharmacological effects. AMB has been proven to have an evident therapeutic effect on ischemic cerebrovascular diseases, including cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism underlying AMB in CIRI remains unclear. Aim of the study: This study aimed to investigate the potential role of AMB in CIRI through a comprehensive approach of network pharmacology and in vivo experimental research. Methods: The intersection genes of drugs and diseases were obtained through analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Gene Expression Omnibus (GEO) database. The proteinprotein interaction (PPI) network was created through the string website. Meanwhile, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out using R studio, and thereafter the key genes were screened. Then, the molecular docking prediction was made between the main active ingredients and target genes, and hub genes with high binding energy were obtained. In addition, molecular dynamic (MD) simulation was used to validate the result of molecular docking. Based on the results of network pharmacology, we used animal experiments to verify the predicted hub genes. First, the rat middle cerebral artery occlusion and reperfusion (MACO/R) model was established and the effective dose of AMB in CIRI was determined by behavioral detection and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Then the target proteins corresponding to the hub genes were measured by Western blot. Moreover, the level of neuronal death was measured using hematoxylin and eosin (HE) and Nissl staining. Results: Based on the analysis of the TCMSP database and GEO database, a total of 62 intersection target genes of diseases and drugs were obtained. The KEGG enrichment analysis showed that the therapeutic effect of AMB on CIRI might be realized through the advanced glycation endproduct-the receptor of advanced glycation endproduct (AGE-RAGE) signaling pathway in diabetic complications, nuclear factor kappa-B (NF-kappa B) signaling pathway and other pathways. Molecular docking results showed that the active ingredients of AMB had good binding potential with hub genes that included Prkcb, Ikbkb, Gsk3b, Fos and Rela. Animal experiments showed that AWE (60 g/kg) could alleviate CIRI by regulating the phosphorylation of PKC(3, IKK(3, GSK3(3, c-Fos and NF kappa B p65 proteins. Conclusion: AMB exerts multi-target and multi-pathway effects against CIRI, and the underlying mechanism may be related to anti-apoptosis, anti-inflammation, anti-oxidative stress and inhibiting calcium overload. |
| WOS关键词 | C-FOS ; BRAIN-BARRIER ; HIPPOCAMPUS ; ACTIVATION ; EXPRESSION ; COMBINATION ; COMPONENTS ; APOPTOSIS ; STRESS ; JUNB |
| 资助项目 | Open Fund of State Key Laboratory of Tea Plant Biology and Utilization[SKLTOF20230102] ; Scientific research project of Anhui Provincial Health Commission[AHWJ2022b009] ; Natural Science Research Project of Colleges and Universities of Anhui Province[2023AH052594] ; Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, P.R. China (Anhui Medical University)[KFJJ-2021-14] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001293391000001 |
| 出版者 | ELSEVIER IRELAND LTD |
| 资助机构 | Open Fund of State Key Laboratory of Tea Plant Biology and Utilization ; Scientific research project of Anhui Provincial Health Commission ; Natural Science Research Project of Colleges and Universities of Anhui Province ; Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, P.R. China (Anhui Medical University) |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/136034]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Yang, Wulin; Wang, Yijun; Luo, Shengyong |
| 作者单位 | 1.Anhui Med Univ, Sch Basic Med, Dept Pharmacol, Hefei 230031, Peoples R China 2.Anhui Acad Med Sci, Anhui Med Coll, Hefei 230061, Peoples R China 3.Anhui Agr Univ, State Key Lab Tea Plant Biol & Utilizat, 130 Changjiang West Rd, Hefei 230036, Peoples R China 4.Chinese Acad Sci, Anhui Prov Key Lab Med Phys & Technol, Inst Hlth & Med Technol, Hefei Inst Phys Sci, Hefei 230031, Peoples R China 5.Anhui Med Coll, Dept Pharm, Hefei 230601, Peoples R China 6.Anhui Med Univ, Basic Med Coll, Dept Pharmacol, Hefei 230032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Rui,Lou, Qi,Ji, Tingting,et al. Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification[J]. JOURNAL OF ETHNOPHARMACOLOGY,2024,329. |
| APA | Li, Rui.,Lou, Qi.,Ji, Tingting.,Li, Yincan.,Yang, Haoran.,...&Luo, Shengyong.(2024).Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification.JOURNAL OF ETHNOPHARMACOLOGY,329. |
| MLA | Li, Rui,et al."Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification".JOURNAL OF ETHNOPHARMACOLOGY 329(2024). |
入库方式： OAI收割
来源：合肥物质科学研究院
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