综合代谢组学和网络药理学分析，揭示金刚烷胺苷 A 对非酒精性脂肪肝的保护作用

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology Pub Date : 2024-10-30 DOI:10.1016/j.ejphar.2024.177074

Sijia Jiang , Xiaoxu Fan , Jian Hua , Shuangqiao Liu , Yingtong Feng , Danyue Shao , Yiwei Shen , Zhen Wang , Xuehua Yan , Jingxia Wang

{"title":"综合代谢组学和网络药理学分析，揭示金刚烷胺苷 A 对非酒精性脂肪肝的保护作用","authors":"Sijia Jiang , Xiaoxu Fan , Jian Hua , Shuangqiao Liu , Yingtong Feng , Danyue Shao , Yiwei Shen , Zhen Wang , Xuehua Yan , Jingxia Wang","doi":"10.1016/j.ejphar.2024.177074","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo.</div></div><div><h3>Methods</h3><div>First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound–target networks and validated by molecular docking and western blotting.</div></div><div><h3>Results</h3><div>CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets.</div></div><div><h3>Conclusion</h3><div>This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. <span>Furthermore</span>, it provides evidence supporting the potential use of <span>CA</span> in the long-term prevention of NAFLD.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177074"},"PeriodicalIF":4.2000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Integrated metabolomics and network pharmacology analysis to reveal the protective effect of Complanatoside A on nonalcoholic fatty liver disease\",\"authors\":\"Sijia Jiang , Xiaoxu Fan , Jian Hua , Shuangqiao Liu , Yingtong Feng , Danyue Shao , Yiwei Shen , Zhen Wang , Xuehua Yan , Jingxia Wang\",\"doi\":\"10.1016/j.ejphar.2024.177074\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo.</div></div><div><h3>Methods</h3><div>First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound–target networks and validated by molecular docking and western blotting.</div></div><div><h3>Results</h3><div>CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets.</div></div><div><h3>Conclusion</h3><div>This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. <span>Furthermore</span>, it provides evidence supporting the potential use of <span>CA</span> in the long-term prevention of NAFLD.</div></div>\",\"PeriodicalId\":12004,\"journal\":{\"name\":\"European journal of pharmacology\",\"volume\":\"985 \",\"pages\":\"Article 177074\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014299924007647\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299924007647","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

摘要

导言：非酒精性脂肪肝（NAFLD）发病率的上升和严重后果促使人们寻求预防性药物。蟾酥苷 A（CA）是黄芪精液中的显著黄酮类化合物，是一种作用于肝经的传统中草药，被广泛用于治疗肝脏疾病。CA 在体外已被证明具有相当的降脂和保肝作用。然而，CA在预防非酒精性脂肪肝方面的功效尚未在体内得到证实：方法：首先，使用高脂饮食（HFD）小鼠模型评估CA对非酒精性脂肪肝的疗效。方法：首先，利用高脂饮食（HFD）小鼠模型评估CA对非酒精性脂肪肝的有效性；其次，采用代谢组学和网络药理学相结合的策略研究CA对非酒精性脂肪肝的保护机制。代谢组学分析确定了差异代谢物，代谢通路分析由 MetaboAnalyst 完成。通过网络药理学获得了潜在的治疗靶点。最后，通过化合物-靶点网络确定了关键靶点，并通过分子对接和免疫印迹进行了验证：结果：CA主要通过减少高脂血症小鼠的肝脏脂质积累来预防非酒精性脂肪肝。代谢组学确定了 22 个 CA 治疗非酒精性脂肪肝的潜在生物标志物，主要涉及甘油磷脂和花生四烯酸代谢。网络药理学确定了51个潜在靶点。共同分析显示，白蛋白、过氧化物酶体增殖激活受体α、视黄醇X受体α、白细胞介素-6和肿瘤坏死因子α是关键靶点：本实验揭示了 CA 主要通过调节过氧化物酶体增殖激活受体-α/视黄醇 X 受体α途径对非酒精性脂肪肝具有预防作用。此外，该实验还为 CA 在长期预防非酒精性脂肪肝方面的潜在应用提供了证据支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Integrated metabolomics and network pharmacology analysis to reveal the protective effect of Complanatoside A on nonalcoholic fatty liver disease

查看原文本刊更多论文

Integrated metabolomics and network pharmacology analysis to reveal the protective effect of Complanatoside A on nonalcoholic fatty liver disease

Introduction

The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo.

Methods

First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound–target networks and validated by molecular docking and western blotting.

Results

CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets.

Conclusion

This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. Furthermore, it provides evidence supporting the potential use of CA in the long-term prevention of NAFLD.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.