Na An, Dongxing Zhang, Jile Xin, Xinyi Zhang, Zhijuan Zhang, Ligang Ma, Le Zhao, Huimin Wu, Weisheng Feng, Xiaoke Zheng
{"title":"通过调节 HIF-1 通路从硅镍散中鉴定出的四化合物鸡尾酒的抗抑郁特性","authors":"Na An, Dongxing Zhang, Jile Xin, Xinyi Zhang, Zhijuan Zhang, Ligang Ma, Le Zhao, Huimin Wu, Weisheng Feng, Xiaoke Zheng","doi":"10.2174/0115734099305381240613114436","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Si-Ni-San (SNS) is the formula prescription of Traditional Chinese Medicine (TCM) with anti-depression properties, but its underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study provides novel approaches for the study of Traditional Chinese Medicine (TCM) and offers new opportunities for exploring the pharmacological properties of SNS.</p><p><strong>Methods: </strong>The ingredients in SNS implicated in the treatment of depression were identified and studied using network pharmacology. SwissTargetPrediction and molecular docking were used to study the interaction of SNS ingredients and their targets. The protective effect of these ingredients and their cocktail in rat pheochromocytoma cells (PC12) exposed to corticosterone (Cor) were evaluated using the CCK-8 assay, Hoechst 33342 staining, 2',7'-dichlorodihydro fluorescein diacetate (H2DCFDA) staining, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and in-cell Western analysis.</p><p><strong>Results: </strong>The network pharmacology study showed that the HIF-1 signaling pathway was the most crucial pathway implicated in the anti-depressive property of SNS. MAPK1 (ERK2), MAPK3 (ERK1), AKT1, VEGFA, STAT3, and EGF were identified as hub target proteins in the HIF-1 signaling pathway. Quercetin, naringenin, licochalcone A, and kaempferol from SNS, which targeted the six proteins mentioned above, were used to create a cocktail. This cocktail exerted protective properties, decreased the oxidative stress in PC12 exposed to Cor, and successfully regulated the expressions of AKT1, p-AKT1, ERK1, ERK2, p-ERK1/2, STAT3, p- STAT3, and VEGFA induced by Cor exposure. The SwissTargetPrediction and molecular docking study showed that the cocktail may regulate the HIF-1 signaling pathway by directly binding with AKT1 and MAPK1.</p><p><strong>Conclusion: </strong>The cocktail from SNS comprised of quercetin, naringenin, licochalcone A, and kaempferol exerts anti-depression potentiality by modulating the HIF-1 signaling pathway via direct interactions with AKT1 and MAPK1.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antidepressant Properties of a Four-compound Cocktail Identified from Si-Ni-San by HIF-1 Pathway Modulation.\",\"authors\":\"Na An, Dongxing Zhang, Jile Xin, Xinyi Zhang, Zhijuan Zhang, Ligang Ma, Le Zhao, Huimin Wu, Weisheng Feng, Xiaoke Zheng\",\"doi\":\"10.2174/0115734099305381240613114436\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Si-Ni-San (SNS) is the formula prescription of Traditional Chinese Medicine (TCM) with anti-depression properties, but its underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study provides novel approaches for the study of Traditional Chinese Medicine (TCM) and offers new opportunities for exploring the pharmacological properties of SNS.</p><p><strong>Methods: </strong>The ingredients in SNS implicated in the treatment of depression were identified and studied using network pharmacology. SwissTargetPrediction and molecular docking were used to study the interaction of SNS ingredients and their targets. The protective effect of these ingredients and their cocktail in rat pheochromocytoma cells (PC12) exposed to corticosterone (Cor) were evaluated using the CCK-8 assay, Hoechst 33342 staining, 2',7'-dichlorodihydro fluorescein diacetate (H2DCFDA) staining, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and in-cell Western analysis.</p><p><strong>Results: </strong>The network pharmacology study showed that the HIF-1 signaling pathway was the most crucial pathway implicated in the anti-depressive property of SNS. MAPK1 (ERK2), MAPK3 (ERK1), AKT1, VEGFA, STAT3, and EGF were identified as hub target proteins in the HIF-1 signaling pathway. Quercetin, naringenin, licochalcone A, and kaempferol from SNS, which targeted the six proteins mentioned above, were used to create a cocktail. This cocktail exerted protective properties, decreased the oxidative stress in PC12 exposed to Cor, and successfully regulated the expressions of AKT1, p-AKT1, ERK1, ERK2, p-ERK1/2, STAT3, p- STAT3, and VEGFA induced by Cor exposure. The SwissTargetPrediction and molecular docking study showed that the cocktail may regulate the HIF-1 signaling pathway by directly binding with AKT1 and MAPK1.</p><p><strong>Conclusion: </strong>The cocktail from SNS comprised of quercetin, naringenin, licochalcone A, and kaempferol exerts anti-depression potentiality by modulating the HIF-1 signaling pathway via direct interactions with AKT1 and MAPK1.</p>\",\"PeriodicalId\":93961,\"journal\":{\"name\":\"Current computer-aided drug design\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current computer-aided drug design\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0115734099305381240613114436\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current computer-aided drug design","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115734099305381240613114436","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景四逆散（SNS）是具有抗抑郁作用的中药方剂，但其作用机制尚不清楚：本研究为中药研究提供了新方法，并为探索四逆散的药理特性提供了新机会：方法：采用网络药理学方法确定并研究了SNS中与治疗抑郁症有关的成分。方法：采用网络药理学方法确定并研究了SNS中与治疗抑郁症有关的成分，并利用SwissTargetPrediction和分子对接技术研究了SNS成分与其靶点的相互作用。利用 CCK-8 试验、Hoechst 33342 染色、2',7'-二氯二氢荧光素二乙酸酯（H2DCFDA）染色、2,2-二苯基-1-苦基肼（DPPH）自由基清除试验和细胞内 Western 分析，评估了这些成分及其鸡尾酒对暴露于皮质酮（Cor）的大鼠嗜铬细胞瘤细胞（PC12）的保护作用：网络药理学研究表明，HIF-1 信号通路是 SNS 抗抑郁作用的最关键通路。MAPK1（ERK2）、MAPK3（ERK1）、AKT1、VEGFA、STAT3和EGF被确定为HIF-1信号通路的枢纽靶蛋白。我们利用 SNS 中针对上述六种蛋白的槲皮素、柚皮素、甘草查耳酮 A 和山奈酚制成了一种鸡尾酒。该鸡尾酒具有保护作用，可降低暴露于Cor的PC12的氧化应激，并成功调节Cor诱导的AKT1、p-AKT1、ERK1、ERK2、p-ERK1/2、STAT3、p- STAT3和VEGFA的表达。SwissTarget预测和分子对接研究表明，鸡尾酒可能通过直接与AKT1和MAPK1结合来调节HIF-1信号通路：由槲皮素、柚皮素、甘草查耳酮 A 和山奈酚组成的 SNS 鸡尾酒通过与 AKT1 和 MAPK1 的直接相互作用调节 HIF-1 信号通路，从而发挥抗抑郁的潜力。
Antidepressant Properties of a Four-compound Cocktail Identified from Si-Ni-San by HIF-1 Pathway Modulation.
Background: Si-Ni-San (SNS) is the formula prescription of Traditional Chinese Medicine (TCM) with anti-depression properties, but its underlying mechanisms remain unclear.
Objective: This study provides novel approaches for the study of Traditional Chinese Medicine (TCM) and offers new opportunities for exploring the pharmacological properties of SNS.
Methods: The ingredients in SNS implicated in the treatment of depression were identified and studied using network pharmacology. SwissTargetPrediction and molecular docking were used to study the interaction of SNS ingredients and their targets. The protective effect of these ingredients and their cocktail in rat pheochromocytoma cells (PC12) exposed to corticosterone (Cor) were evaluated using the CCK-8 assay, Hoechst 33342 staining, 2',7'-dichlorodihydro fluorescein diacetate (H2DCFDA) staining, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and in-cell Western analysis.
Results: The network pharmacology study showed that the HIF-1 signaling pathway was the most crucial pathway implicated in the anti-depressive property of SNS. MAPK1 (ERK2), MAPK3 (ERK1), AKT1, VEGFA, STAT3, and EGF were identified as hub target proteins in the HIF-1 signaling pathway. Quercetin, naringenin, licochalcone A, and kaempferol from SNS, which targeted the six proteins mentioned above, were used to create a cocktail. This cocktail exerted protective properties, decreased the oxidative stress in PC12 exposed to Cor, and successfully regulated the expressions of AKT1, p-AKT1, ERK1, ERK2, p-ERK1/2, STAT3, p- STAT3, and VEGFA induced by Cor exposure. The SwissTargetPrediction and molecular docking study showed that the cocktail may regulate the HIF-1 signaling pathway by directly binding with AKT1 and MAPK1.
Conclusion: The cocktail from SNS comprised of quercetin, naringenin, licochalcone A, and kaempferol exerts anti-depression potentiality by modulating the HIF-1 signaling pathway via direct interactions with AKT1 and MAPK1.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
