{"title":"通过网络药理学预测,发现黄连对肝脏再生的潜在药理作用机制。","authors":"Wei Liu, Wenyu Wang, Chenglong Tian, Ming-Zhong Sun, Shuqing Liu, Qinlong Liu","doi":"10.4196/kjpp.2024.28.5.479","DOIUrl":null,"url":null,"abstract":"<p><p>Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and <i>in vivo</i> experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"479-491"},"PeriodicalIF":1.6000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362001/pdf/","citationCount":"0","resultStr":"{\"title\":\"Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration.\",\"authors\":\"Wei Liu, Wenyu Wang, Chenglong Tian, Ming-Zhong Sun, Shuqing Liu, Qinlong Liu\",\"doi\":\"10.4196/kjpp.2024.28.5.479\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and <i>in vivo</i> experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.</p>\",\"PeriodicalId\":54746,\"journal\":{\"name\":\"Korean Journal of Physiology & Pharmacology\",\"volume\":\"28 5\",\"pages\":\"479-491\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362001/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Korean Journal of Physiology & Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4196/kjpp.2024.28.5.479\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Korean Journal of Physiology & Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4196/kjpp.2024.28.5.479","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
改善肝脏再生(LR)仍然是一个医学问题,目前缺乏安全有效的肝脏再生药物。三药是一种传统中药。然而,SY治疗LR的潜在作用机制尚未完全阐明。为了探索SY对LR的作用机制,我们进行了一系列的网络药理分析、分子对接和小鼠体内实验验证。结果发现,SY的9个化合物和30个预测靶基因与LR的治疗作用相关。与模型组相比,苏木精和伊红染色显示,术前药物干预的小鼠术后肝细胞气泡较少,形态相对规则。此外,血清丙氨酸转氨酶和天冬氨酸氨基转移酶水平降低,免疫组化显示增殖细胞核抗原阳性率升高,Western 印迹显示磷酸蛋白激酶 B(AKT)/AKT 比值下调,血管内皮生长因子 A(VEGFA)表达水平上调。本研究探讨了 SY 的主要活性成分 dioscin 及其对 LR 的潜在治疗作用。它能修复手术后受损的肝脏,促进肝细胞增殖。其作用机制包括降低 AKT 磷酸化水平和上调 VEGFA 表达水平。因此,本研究为进一步研究 SY 促进 LR 的机制提供了新的方向。
Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration.
Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.
期刊介绍:
The Korean Journal of Physiology & Pharmacology (Korean J. Physiol. Pharmacol., KJPP) is the official journal of both the Korean Physiological Society (KPS) and the Korean Society of Pharmacology (KSP). The journal launched in 1997 and is published bi-monthly in English. KJPP publishes original, peer-reviewed, scientific research-based articles that report successful advances in physiology and pharmacology. KJPP welcomes the submission of all original research articles in the field of physiology and pharmacology, especially the new and innovative findings. The scope of researches includes the action mechanism, pharmacological effect, utilization, and interaction of chemicals with biological system as well as the development of new drug targets. Theoretical articles that use computational models for further understanding of the physiological or pharmacological processes are also welcomed. Investigative translational research articles on human disease with an emphasis on physiology or pharmacology are also invited. KJPP does not publish work on the actions of crude biological extracts of either unknown chemical composition (e.g. unpurified and unvalidated) or unknown concentration. Reviews are normally commissioned, but consideration will be given to unsolicited contributions. All papers accepted for publication in KJPP will appear simultaneously in the printed Journal and online.