目的: 基于网络药理学和分子对接技术探讨连陈汤治疗痰湿型肥胖的作用机制。方法: 运用中药系统药理学数据库与分析平台（TCMSP）获取连陈汤有效活性成分及作用靶点。通过人类基因组数据库（GeneCards）、药物靶标数据库（TTD）和在线人类孟德尔遗传数据库（OMIMO）获取疾病靶点。通过证候本体数据库及多维定量关联计算平台（SoFDA）获取痰湿型相关靶点。通过Cytoscape 3.10.1软件构建网络,拓扑分析筛选关键活性成分、核心靶点。使用微生信平台对潜在作用靶点进行基因主体（GO）功能富集和京都基因与基因组百科全书（KEGG）信号通路富集分析。利用AutoDockVina软件对成分和靶点进行分子对接。结果: 获得连陈汤靶点148个、疾病靶点9958个、痰湿型靶点896个。将靶点取交集,获得潜在作用靶点106个。网络拓扑分析获得甘油、米桔素、穆坪马兜铃酰胺为关键活性成分。PPI网络分析筛选出MC4R、PPARG、FTO、GHRL等活跃的靶点。GO功能富集分析显示,包括生物学过程、细胞组件及分子功能3个部分。KEGG通路富集分析显示,靶点主要富集在胰岛素抵抗等相关通路。结论: 连陈汤可能通过甘油、米桔素、穆坪马兜铃酰胺等关键活性成分作用于MC4R、PPARG、FTO、GHRL等核心靶点调控胰岛素抵抗通路、胰岛素信号通路等信号通路发挥治疗痰湿型肥胖的作用。
Objective: To explore the mechanism of action of Lianchen Decoction in treating phlegm-dampness obesity based on network pharmacology and molecular docking technology. Methods: TCMSP was used to obtain the active ingredients and target of Lianchen Decoction. Disease targets were obtained through GeneCards, TTD, and OMIM. The related targets of phlegm-dampness type were obtained by SoFDA. The network was constructed using Cytoscape3.10.1 software to screen key active ingredients and core targets through topological analysis. GO function enrichment and KEGG signaling pathway enrichment analysis were performed on potential targets using Weisheng platform. AutoDockVina software was used for molecular docking of components and targets. Results: 148 targets, 9958 targets of disease and 896 targets of phlegm-dampness were obtained. The targets were intersected and 106 potential targets were obtained. The network topology analysis showed that glycerol, citromitin and mupingaristolamide were the key active components. PPI network analysis screened out MC4R, PPARG, FTO, GHRL and other active targets. GO functional enrichment analysis showed that there were three parts: biological process, cell components and molecular function. KEGG pathway enrichment analysis showed that the target was mainly concentrated in insulin resistance related pathways. Conclusion: Lianchen Decoction may act on MC4R, PPARG, FTO, GHRL and other core targets to regulate insulin resistance pathway and insulin signaling pathway through the action of key active ingredients such as glycerol, citromitin, mupingaristolamide, and play a role in the treatment of phlegm and dampness type obesity.
[1] Chen X,Huang W,Wei D,et al.Clinical Effect of Catgut Implantation at Acupoints for the Treatment of Simple Obesity: A Multicentre Randomized Controlled Trial[J]. Medicine(Baltimore),2020,99(48):e23390.
[2] The Lancet.Obesity: A Growing Threat to Health in China[J]. Lancet,2014,384(9945):716.
[3] 张质夫,王振华. 肥胖的危害[J]. 中国社区医师(医学专业),2012,14(20):346 .
[4] Garvey WT, Mechanick JI, Brett EM, et al.American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity[J]. Endocr Pract,2016,22:1-203.
[5] 田芳,陈婷. 半夏现代研究进展[J]. 广东化工,2022,49(14):75-76,107.
[6] 刘翠翠. 连陈汤治疗脾虚湿阻型肥胖的疗效观察及对肠道菌群的影响[D]. 哈尔滨:黑龙江中医药大学,2020.
[7] Yu M, Han S, Wang M, et al.Baicalin Protects Against Insulin Resistance and Metabolic Dysfunction Through Activation of GALR2/GLUT4 Signaling[J]. Phytomedicine,2022,95:153869.
[8] 董传莹,薛飞,郝瑞,等. 川陈皮素对脂多糖诱导的牙周膜细胞损伤和NOD样受体蛋白3炎性通路的影响[J].中国临床药理学杂志,2022,38(17):2013-2017.
[9] 韩思婕,潘翔,朱芊芊,等. 茯苓多糖调节2型糖尿病模型大鼠肝脏糖异生的机制研究[J]. 中国药房,2022,33(13):1581-158.
[10] 蔡然,宋轶. 基于网络药理学探讨黄连防治2型糖尿病的作用机制[J]. 湖南中医杂志,2022,38(6):158-163.
[11] Dong Z, Liu MT, Zou XL, et al.Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of Action of Macleaya Cordata(Willd.) R. Br. in the Treatment of Bovine Hoof Disease[J]. Vet Sci,2021,9(1):11.
[12] 姜平,戴洁梅,魏凯,等. 基于网络药理学及分子对接技术探究复方雷公藤逐痛颗粒干预类风湿关节炎的作用机制[J]. 上海中医药杂志,2022,56(9):21-31.
[13] 中国医疗保健国际交流促进会营养与代谢管理分会,中国营养学会临床营养分会,中华医学会糖尿病学分会,等. 中国超重／肥胖医学营养治疗指南(2021)[J]. 中国医学前沿杂志(电子版),2021,3(11):1-55.
[14] Haidar Y, Cosman B.Obesity Epidemiology[J]. ClinColon Rectal Surg,2011,24(4):205-210.
[15] Scully T.Obesity[J]. Nature,2014,508(7496):S49.
[16] 中国居民肥胖防治专家共识[J]. 中国预防医学志,2022,23(5):321-339.
[17] 燕宪涛,陈大卫,顾瑞霞. 中药复方治疗肥胖作用机制的研究进展[J]. 世界科学技术-中医药现代化,2022,24(8):2947-2956.
[18] 曲伸,陆灏,宋勇峰. 基于临床的肥胖症多学科诊疗共识(2021年版)[J]. 中华肥胖与代谢病电子杂志,2021,7(4):211-226.
[19] 田景梅,张扬,张云峰,等. 黄酮类调节脂肪平衡与降低心血管疾病发生机制的研究进展[J]. 安徽农业科学,2012,40(9):5259-5262,5351.
[20] 王丽,孙蓉. 与功效、毒性相关的半夏化学成分研究进展[J]. 中药药理与临床,2009,25(5):101,17.
[21] 崔鹤蓉,王睿林,郭文博,等. 茯苓的化学成分、药理作用及临床应用研究进展[J]. 西北药学杂志,2019,34(5):694-700.
[22] 张耀峰. 甘草及其活性成分的药理活性研究进展[J]. 中医临床研究,2019,11(9):141-142.
[23] 梁亮,魏晓莉,孙彭利,等. 新型黑皮质素4受体激动剂减肥作用研究[J]. 解放军药学学报,2009,25(5):386-390.
[24] 仝雪薇,冶学燕,刘春燕,等. 2型糖尿病合并肥胖患者外周血PPARG、CIDEA、ECHDC3、CGN mRNA表达与血脂水平的关系研究[J]. 深圳中西医结合杂志,2021,31(6):4-8,199.
[25] 黄春晓,郭雪莹,相新新. m6A去甲基化酶FTO在脂质代谢中的研究进展[J]. 中国临床新医学,2023,16(11):1195-1199.
[26] Sahu B, Bal NC.Adipokines from White a Dipose Tissue in Regulation of Whole Body Energy Homeostasis[J]. Biochimie,2023,204:92-107.
[27] Tschop M, Smiley DL.Ghrelin Induces Adiposity in Rodents[J]. Nature,2000,407(6806):908-913.
[28] 苏庆民,王琦. 肥胖人痰湿型体质血脂、血糖、胰岛素及红细胞Na~+—K~+—ATP酶活性的检测[J]. 中国中医基础医学杂志,1995(2):39-41.
[29] 刘长锁,申竹芳. 游离脂肪酸与胰岛素抵抗[J]. 中国药理学通报,2005(2):145-149.
[30] 朱大元,黄宝山. 马兜铃属植物的化学、药理和临床[J]. 国外医学. 药学分册,1979(2):83-86,76.
[31] 孟祥河. 功能性甘油二酯的酶促酯化合成及其减肥功能的研究[D]. 无锡:江南大学,2004.
[32] 李经纬等主编. 中医大词典[M]. 第2版. 北京:人民卫生出版社,2004:1948.
