Mechanism of <i>Gynostemma pentaphyllum</i> on Prevention and Treatment of Obesity Based on Network Pharmacology and Molecular Docking Technology

SU Yao; WANG Lan; CHANG Xiangna; GONG Pin; YANG Wenjuan; CUI Dandan

doi:10.13386/j.issn1002-0306.2021070083

Volume 43 Issue 4

Feb. 2022

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Science and Technology of Food Industry > 2022 > 43(4): 12-23. > DOI: 10.13386/j.issn1002-0306.2021070083

SU Yao, WANG Lan, CHANG Xiangna, et al. Mechanism of Gynostemma pentaphyllum on Prevention and Treatment of Obesity Based on Network Pharmacology and Molecular Docking Technology[J]. Science and Technology of Food Industry, 2022, 43(4): 12−23. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021070083.

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Mechanism of Gynostemma pentaphyllum on Prevention and Treatment of Obesity Based on Network Pharmacology and Molecular Docking Technology

College of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China

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Received Date: July 06, 2021
Available Online: December 15, 2021

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Abstract

Objective: The study revealed the material basis and potential mechanism of Gynostemma pentaphyllum for preventing obesity through network pharmacology and molecular docking technology. Methods: Using TCMSP database combined with literatures to supplement the screening of active ingredients. Using Pubchem and Swiss target prediction databases to collect the targets of active ingredients of Gynostemma pentaphyllum. Using GeneCards, OMIM and DurgBank databases to obtain obesity targets. Taking the intersection of Gynostemma pentaphyllum action targets and disease targets as Gynostemma pentaphyllum prevention and treatment targets for obesity, and using Cytoscape 3.7.2 software to construct a drug-compound-target network. The STRING database was used to construct a target protein interaction PPI network to screen core targets, Discovery Studio 3.5 was used to docks the selected core targets with the active ingredient molecules, DAVID database performs GO enrichment and KEGG pathway annotation analysised on intersection targets, and built a component-target-pathway interaction network model based on the above results. Results: A total of 16 compounds including quercetin, 3'-methyleriodictyol, ginsenoside f2, and gypenoside XXVIII were selected as the material basis for the prevention and treatment of obesity in Gynostemma pentaphyllum, and 107 targets for the treatment of obesity, including STAT3, AKT1, VEGFA , SRC, EGFR, MAPK3 and other 38 key targets. The results of molecular docking showed that the top 6 core targets of PPI had good binding activities with the corresponding compounds 3'-methyleriodictyol, Rhamnazin, Ruvoside, Spinasterol, ginsenoside f2, CLR, quercetin, Gypenoside XXVIII, speculate on these components may be the main pharmacodynamic components. GO analysis showed that the prevention and treatment of obesity by Gynostemma pentaphyllum mainly involved biological processes such as cell growth, proliferation and metabolic processes, molecular functions such as enzyme binding, protein binding, cellular components such as nucleus and cytoplasm. KEGG pathway enrichment results showed that pathway involving cancer signaling pathways, proteoglycan pathways in cancer, PI3K-Akt signaling pathways, and HIF-1 signaling pathways. Conclusion: This study initially revealed that Gynostemma pentaphyllum could affect the proliferation and differentiation of adipocytes, glucose and lipid metabolism, and maintain body homeostasis through multiple components, multiple targets, and multiple pathways to achieve obesity prevention and treatment, would provide a basis for further research on the effective ingredients and molecular mechanisms.
- obesity,
- Gynostemma pentaphyllum,
- network pharmacology,
- molecular docking,
- mechanism

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[1]	JURA M, KOZAK L P. Obesity and related consequences to ageing[J]. Age (Dordr),2016,38(1):23. doi: 10.1007/s11357-016-9884-3
[2]	ORTEGA F B, LAVIE C J, BLAIR S N. Obesity and cardiovascular disease[J]. Circ Res,2016,118(11):1752−1770. doi: 10.1161/CIRCRESAHA.115.306883
[3]	TAHERGORABI Z, KHAZAEI M, MOODI M, et al. From obesity to cancer: A review on proposed mechanisms[J]. Cell Biochem Funct,2016,34(8):533−545. doi: 10.1002/cbf.3229
[4]	顾志敏. 降脂中药的研究进展[C]//天津: 第十三届中国科协年会论文集. 中国科协, 2011: 1−4. GU Z M. Research progress of lipid-lowering Chinese medicine[C]// Tianjin: Proceedings of the 13th Annual Conference of China Association for Science and Technology. China Association for Science and Technology, 2011: 1−4.
[5]	张欣怡, 夏明明. 绞股蓝化学成分的降血脂机制研究进展[J]. 光明中医,2020,345(8):161−164. [ZHANG X Y, XIA M M. Research progress on the mechanism of lowering blood lipids of the chemical constituents of Gynostemma pentaphyllum[J]. Guangming Traditional Chinese Medicine,2020,345(8):161−164.
[6]	沈子琳, 王振波, 侯会芳, 等. 绞股蓝的化学成分和药理作用及应用研究新进展[J]. 人参研究,2020,32(5):59−64. [SHEN Z L, WANG Z B, HOU H F, et al. The chemical constituents and pharmacological effects of Gynostemma pentaphyllum and the new progress of application research[J]. Ginseng Research,2020,32(5):59−64.
[7]	田梦菲, 陈涤平, 李文林, 等. 肥胖与中医体质类型相关性的研究进展[J]. 广东医学,2018,1(39):68−70. [TIAN M F, CHEN D P, LI W L, et al. Research progress on the correlation between obesity and traditional Chinese medical constitution[J]. Guangdong Medicine,2018,1(39):68−70.
[8]	JIAN H, SU H, WANG C, et al. Hypolipidemic mechanism of gypenosides via inhibition of pancreatic lipaseand reduction in cholesterol micellar solubility[J]. European Food Research and Technology,2016,242(3):305−312. doi: 10.1007/s00217-015-2540-9
[9]	汪巍. 胆汁酸通路介导的绞股蓝总皂苷调节糖脂代谢的作用机制研究[D]. 遵义: 遵义医学院, 2017. WANG W. Study on the mechanism of Gynostemma pentaphyllum by bile acid pathway in regulating glucose and lipid metabolism[D]. Zunyi: Zunyi Medical College, 2017.
[10]	CHOI I, PARK Y, CHOI H, et al. Anti-adipogenic activity of rutin in 3T3-L1 cells and mice fed with high-fat diet[J]. Biofactors,2006,26(4):273−281. doi: 10.1002/biof.5520260405
[11]	KOJTA I, CHACIŃSKA M, BŁACHNIO-ZABIELSKA A. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance[J]. Nutrients,2020,12(5):1305. doi: 10.3390/nu12051305
[12]	张敏. 槲皮素调节胆固醇代谢作用的途径分析[D]. 北京: 解放军军事医学科学院, 2016. ZHANG M. Analysis of the pathways of quercetin regulating cholesterol metabolism[D]. Beijing: Chinese Academy of Military Medical Sciences, 2016.
[13]	杨夏, 冯颖淑, 童珊珊, 等. 降血脂多糖活性机制及构效关系研究进展[J]. 中国中药杂志,2018,43(20):4011−4018. [YANG X, FENG Y S, TONG S S, et al. Progress in research on the mechanism and structure-activity relationship of lipid-lowering polysaccharide activity[J]. Chinese Journal of Chinese Materia Medica,2018,43(20):4011−4018.
[14]	ZHANG W, BAI Y, WANG Y, et al. Polypharmacology in drug discovery: A review from systems pharmacology perspective[J]. Curr Pharm Des,2016,22(21):3171−3181. doi: 10.2174/1381612822666160224142812
[15]	王乐琪, 张云帆, 李莎莎, 等. 丹参治疗微循环障碍作用机制的“成分-靶点-通路”多层次互作网络模型研究[J]. 中草药,2020,51(2):439−450. [WANG L Q, ZHANG Y F, LI S S, et al. Research on the “component-target-pathway” multi-level interaction network model of the mechanism of action of Danshen in the treatment of microcirculation disorders[J]. Chinese Herbal Medicine,2020,51(2):439−450.
[16]	谈钰濛, 胡骏, 倪青. 黄芪防治糖尿病肾病的网络药理学研究[J]. 世界中西医结合杂志,2020,15(8):1480−1489. [TAN Y M, HU J, NI Q. A network pharmacology study on the prevention and treatment of diabetic nephropathy by Astragalus[J]. World Journal of Integrated Traditional Chinese and Western Medicine,2020,15(8):1480−1489.
[17]	LI Y, ZHANG J, CHEN X, et al. Systems pharmacology to decipher the combinational anti-migraine effects of Tianshu formula[J]. J Ethnopharmacol,2015,174:45−56. doi: 10.1016/j.jep.2015.07.043
[18]	鲍凤霞, 陶泠雪, 章海燕. 绞股蓝有效成分的药理作用研究进展[J]. 中国新药与临床杂志,2018,1(3):11−17. [BAO F X, TAO L X, ZHANG H Y. Research progress on the pharmacological effects of the active ingredients of Gynostemma pentaphyllum[J]. Chinese Journal of New Drugs and Clinics,2018,1(3):11−17.
[19]	史琳, 王志成, 时圣明, 等. 绞股蓝皂苷水解产物化学成分和药理作用研究进展[J]. 药物评价研究,2017,40(5):711−716. [SHI L, WANG Z C, SHI S M, et al. Research progress on the chemical constituents and pharmacological effects of hydrolysates of gypenosides pentaphyllum[J]. Drug Evaluation Research,2017,40(5):711−716.
[20]	王绍辉, 陈道金, 刘同祥. 绞股蓝化学成分, 药理作用及其体内代谢的研究进展[J]. 世界科学技术:中医药现代化,2015,11(11):2389−2393. [WANG S H, CHEN D J, LIU T X. Research progress on the chemical constituents, pharmacological effects and metabolism of Gynostemma pentaphyllum[J]. World Science and Technology: Modernization of Traditional Chinese Medicine,2015,11(11):2389−2393.
[21]	SZKLARCZYK D, MORRIS J H, COOK H, et al. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible[J]. Nucleic Acids Res,2017,45(1):362−368.
[22]	陈江锋, 林芝娴, 韩孙亚, 等. 基于网络药理学结合分子对接方法探讨绞股蓝治疗非小细胞肺癌的作用机制[J]. 广州中医药大学学报,2020,37,183(3):121−129. [CHEN J F, LIN Z X, HAN S Y, et al. Explore the mechanism of Gynostemma pentaphyllum in the treatment of non-small cell lung cancer based on network pharmacology combined with molecular docking methods[J]. Journal of Guangzhou University of Traditional Chinese Medicine,2020,37,183(3):121−129.
[23]	YASUO N, SEKIJIMA M. Improved method of structure-based virtual screening via interaction-energy-based learning[J]. J Chem Inf Model,2019,59(3):1050−1061. doi: 10.1021/acs.jcim.8b00673
[24]	郭艳芳, 张皓, 朱玲, 等. 槲皮素改善糖尿病肥胖大鼠糖脂代谢紊乱及总胆固醇的作用[J]. 解剖学研究,2018,40(6):49−53. [GUO Y F, ZHANG H, ZHU L, et al. Effects of quercetin on improving glucose and lipid metabolism disorder and total cholesterol in diabetic obese rats[J]. Anatomical Research,2018,40(6):49−53.
[25]	SATO S, MUKAI Y. Modulation of chronic inflammation by quercetin: The beneficial effects on obesity[J]. J Inflamm Res,2020,13:421−431. doi: 10.2147/JIR.S228361
[26]	SIRAJ F M, SATHISHKUMAR N, KIM Y J, et al. Ginsenoside F2 possesses anti-obesity activity via binding with PPARγ and inhibiting adipocyte differentiation in the 3T3-L1 cell line[J]. J Enzyme Inhib Med Chem,2015,30(1):9−14. doi: 10.3109/14756366.2013.871006
[27]	SANCHEZ-GURMACHES J, MARTINEZ CALEJMAN C, JUNG S M, et al. Brown fat organogenesis and maintenance requires AKT1 and AKT2[J]. Mol Metab,2019,23:60−74. doi: 10.1016/j.molmet.2019.02.004
[28]	YUAN X, WEI G, YOU Y, et al. Rutin ameliorates obesity through brown fat activation[J]. Faseb J,2017,31(1):333−345. doi: 10.1096/fj.201600459rr
[29]	JIA X, CHANG T, WILSON T W, et al. Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1[J]. PLoS One, 2012, 7(5): e36610.
[30]	CLEMENTE-POSTIGO M, TINAHONES A, EL BEKAY R, et al. The role of autophagy in white adipose tissue function: Implications for metabolic health[J]. Metabolites,2020,10(5):179. doi: 10.3390/metabo10050179
[31]	徐梦, 马青, 范春兰, 等. STAT3与线粒体电子传递链[J]. 生理科学进展,2019,50(5):366−370. [XU M, MA Q, FAN C L, et al. STAT3 and the mitochondrial electron transport chain[J]. Advances in Physiological Sciences,2019,50(5):366−370. doi: 10.3969/j.issn.0559-7765.2019.05.011
[32]	XU Y, DU J, ZHANG P, et al. MicroRNA-125a-5p mediates 3T3-L1 preadipocyte proliferation and differentiation[J]. Molecules,2018,23(2):317. doi: 10.3390/molecules23020317
[33]	芦小单. 血管内皮生长因子参与脂肪组织分化和能量代谢的调节机制[D]. 长春: 东北师范大学, 2012. LU X D. The regulation mechanism of vascular endothelial growth factor involved in adipose tissue differentiation and energy metabolism[D]. Changchun: Northeast Normal University, 2012.
[34]	JÁSZAI J, SCHMIDT M H H. Trends and challenges in tumor anti-angiogenic therapies[J]. Cells,2019,8(9):1102. doi: 10.3390/cells8091102
[35]	MIYAKE T, PARSONS S J. Functional interactions between Choline kinase α, epidermal growth factor receptor and c-Src in breast cancer cell proliferation[J]. Oncogene,2012,31(11):1431−1441. doi: 10.1038/onc.2011.332
[36]	SONG L, LIU Z, HU H H, et al. Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy[J]. Nat Commun,2020,11(1):5842. doi: 10.1038/s41467-020-19694-w
[37]	PESSENTHEINER A R, DUCASA G M, GORDTS P L S M. Proteoglycans in obesity-associated metabolic dysfunction and meta-inflammation[J]. Front Immunol,2020,11:769. doi: 10.3389/fimmu.2020.00769
[38]	AMIN M N, HUSSAIN M S, SARWAR M S, et al. How the association between obesity and inflammation may lead to insulin resistance and cancer[J]. Diabetes Metab Syndr,2019,13(2):1213−1224. doi: 10.1016/j.dsx.2019.01.041
[39]	CHUANG C C, YANG R S, TSAI K S, et al. Hyperglycemia enhances adipogenic induction of lipid accumulation: Involvement of extracellular signal-regulated protein kinase 1/2, phosphoinositide 3-kinase/Akt, and peroxisome proliferator-activated receptor gamma signaling[J]. Endocrinology,2007,148(9):4267−4275. doi: 10.1210/en.2007-0179
[40]	XIE Y, SHI X, SHENG K, et al. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia[J]. Mol Med Rep,2019,19(2):783−791.
[41]	CAI R, SUN Y, QIMUGE N, et al. Adiponectin AS lncRNA inhibits adipogenesis by transferring from nucleus to cytoplasm and attenuating adiponectin mRNA translation[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2018,1863(4):420−432.
[42]	YEUNG F, RAMÍREZ C M, MATEOS-GOMEZ P A, et al. Nontelomeric role for Rap1 in regulating metabolism and protecting against obesity[J]. Cell Rep,2013,3(6):1847−1856. doi: 10.1016/j.celrep.2013.05.032
[43]	CAI R, TANG G, ZHANG Q, et al. A novel lnc-RNA, named lnc-ORA, is identified by RNA-Seq analysis, and its knockdown inhibits adipogenesis by regulating the PI3K/AKT/mTOR signaling pathway[J]. Cells,2019,8(5):477. doi: 10.3390/cells8050477
[44]	YE J. Mechanisms of insulin resistance in obesity[J]. Front Med,2013,7(1):14−24. doi: 10.1007/s11684-013-0262-6
[45]	KASUNO K, TAKABUCHI S, FUKUDA K, et al. Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAPK and phosphatidylinositol 3-kinase signaling[J]. Biol Chem,2004,279(4):2550−2558. doi: 10.1074/jbc.M308197200
[46]	CIFARELLI V, BEEMAN S C, SMITH G I, et al. Decreased adipose tissue oxygenation associates with insulin resistance in individuals with obesity[J]. J Clin Invest,2020,130(12):6688−6699. doi: 10.1172/JCI141828

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Science and Technology of Food Industry

Mechanism of Gynostemma pentaphyllum on Prevention and Treatment of Obesity Based on Network Pharmacology and Molecular Docking Technology

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