Study on the Anti-obesity Mechanism of Action of <i>Moringa oleifera</i> Lam. Leaves by Network-Based Pharmacology and Molecular Docking Techniques

LI Tingting; GUAN Ya; HONG Zishan; XIE Jing; TIAN Yang

doi:10.13386/j.issn1002-0306.2022090318

Volume 44 Issue 15

Jul. 2023

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Science and Technology of Food Industry > 2023 > 44(15): 34-45. > DOI: 10.13386/j.issn1002-0306.2022090318

LI Tingting, GUAN Ya, HONG Zishan, et al. Study on the Anti-obesity Mechanism of Action of Moringa oleifera Lam. Leaves by Network-Based Pharmacology and Molecular Docking Techniques[J]. Science and Technology of Food Industry, 2023, 44(15): 34−45. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022090318.

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Study on the Anti-obesity Mechanism of Action of Moringa oleifera Lam. Leaves by Network-Based Pharmacology and Molecular Docking Techniques

LI Tingting^{1, 2,},
GUAN Ya¹,
HONG Zishan¹,
XIE Jing^{1, 2, 3, 4, ,},
TIAN Yang^{1, 2, 3, 4, ,}

1.
College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China
2.
National Research Center for Moringa Processing Technology, Kunming 650201, China
3.
Engineering Center for Development and Utilization of Edible and Medicinal Resources, Ministry of Education, Kunming 650201, China
4.
Yunnan Engineening Research Center for Drug and Food Homologous Functioral Food, Kunming 650201, China

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Received Date: October 07, 2022
Available Online: June 05, 2023

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Abstract

Abstract

Objects: In this study, the molecular targets and pathways of anti-obesity of the active ingredients of Moringa oleifera Lam. leaves were predicted and validated by network pharmacology and molecular docking techniques, and the anti-obesity effects of the active ingredients of Moringa oleifera Lam. leaves and their potential mechanisms were investigated. Methods: The active ingredient targets of Moringa oleifera Lam. leaves and obesity-related targets were obtained through PubChem, DisGeNET database and SwissADME, Swiss Target Prediction online prediction platform. The active ingredient targets and obesity-related targets were intersected by Venny 2.0.1 platform, and the key targets were screened out, then the PPI network analysis of the core targets was performed by STRING 11.0 database. The "component-target" interaction network was construct by Cytoscape 3.8.2 software, and the core active ingredients were screened out. GO functional enrichment and KEGG pathway analysis were performed on the core targets by the David database. Finally, molecular docking of pathway enrichment targets to core components was performed using Auto Dock 4.2 software. Results: Fifty active ingredients of Moringa oleifera Lam. leaves were screened, and a total of 126 core targets of Moringa oleifera Lam. leaves anti-obesity were identified, among which the main active ingredients were rhamnetin, cholest-5-en-3-ol, yangmeiin, lignan, etc. GO and KEGG analyses showed that the active ingredients of Moringa oleifera Lam. leaves exerted anti-obesity effects through multiple pathways such as HIF-1, insulin resistance, type 2 diabetes and insulin signalling pathway, and through biological processes such as positive regulation of RNA polymerase II promoter transcription, signalling, positive regulation of gene expression, negative regulation of protein phosphorylation and apoptotic expression. The molecular docking results showed that all 11 core components bound to the targets. Among them, PIK3R1 showed the lowest affinity with rhamnetin (−9.2 kcal/mol), followed by PIK3CA with cholest-5-en-3-ol (−9.1 kcal/mol), PIK3R1 with myricetin (−8.8 kcal/mol), and AKT1 with luteolin (−8.7 kcal/mol). Conclusion: The above results reveals that Moringa oleifera Lam. leaves could aganist obesity through multi-component, multi-target and multi-pathway mecanism. These results will provide a theoretical basis for the in-depth study of the anti-obesity of Moringa oleifera Lam. leaves and its molecular mechanism.
- Moringa oleifera Lam.,
- obesity,
- network pharmacology,
- molecular docking,
- mechanism

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References

[1]	蒋亮, 汤旭磊, 关聪会, 等. 肥胖的药物治疗进展[J]. 中国临床药理学杂志,2021,37(14):1923−1927. [JIANG L, TANG X L, GUAN C H, et al. Advances in drug therapy for obesity[J]. The Chinese Journal of Clinical Pharmacology,2021,37(14):1923−1927. JIANG L, TANG X L, GUAN C H, et al. Advances in drug therapy for obesity[J]. The Chinese Journal of Clinical Pharmacology, 2021, 37(14): 1923-1927.
[2]	王远, 郑雯, 蔡珺珺, 等. 辣木叶黄酮结构分析及其对胰脂肪酶的抑制作用[J]. 食品科学,2018,39(2):31−37. [WANG Y, ZHENG W, CAI J J, et al. Structural analysis and anti-pancreatic lipase activity of flavonoids from Moringa oleifera Lam. leaves[J]. Food Science,2018,39(2):31−37. WANG Y, ZHENG W, CAI J J, et al. Structural analysis and anti-pancreatic lipase activity of flavonoids from Moringa oleifera Lam. leaves[J]. Food Science, 2018, 39(2): 31-37.
[3]	张燕平, 段琼芬, 苏建荣. 辣木的开发与利用[J]. 热带农业科学,2004(4):42−48. [ZHANG Y P, DUAN Q F, SU J R. Horseradish and its utilization: Review[J]. Chinese Journal of Tropical Agriculture,2004(4):42−48. ZHANG Y P, DUAN Q F, SU J R. Horseradish and its utilization: Review[J]. Chinese Journal of Tropical Agriculture, 2004(4): 42-48.
[4]	冀恩惠, 许静, 卫军营, 等. 辣木叶活性成分及其药理作用研究进展[J]. 中国实验方剂学杂志,2021,27(5):214−223. [JI E H, XU J, WEI J Y, et al. Research progress of active constituents and pharmacological effect of Moringa oleifera leaves[J]. Chinese Journal of Experimental Traditional Medical Formulae,2021,27(5):214−223. JI E H, XU J, WEI J Y, et al. Research progress of active constituents and pharmacological effect of Moringa oleifera leaves[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2021, 27(5): 214-223.
[5]	AHMED M E, MOHAMED A, SAMIR E, et al. Moringa oleifera leaves ethanolic extract ameliorates high fat diet-induced obesity in rats[J]. Journal of King Saud University-Science,2021,33(6):101552. doi: 10.1016/j.jksus.2021.101552
[6]	杨学芳, 肖蓉, 廖顺杉, 等. 辣木叶水提取物减缓奥氮平诱导的小鼠糖脂代谢紊乱[J]. 昆明医科大学学报,2021,42(4):20−27. [YANG X F, XIAO R, LIAO S S, et al. Aqueous extract of Moringa oleifera leaves alleviate olanzapine-induced metabolic syndrome in mice[J]. Journal of Kunming Medical University,2021,42(4):20−27. YANG X F, XIAO R, LIAO S S, et al. Aqueous extract of Moringa oleifera leaves alleviate olanzapine-induced metabolic syndrome in mice[J]. Journal of Kunming Medical University, 2021, 42(4): 20-27.
[7]	董笑克, 刘铜华, 常青, 等. 辣木叶醇提物对自发型肥胖型糖尿病大鼠非酒精性脂肪性肝病的影响[J]. 环球中医药,2019,12(8):1149−1153. [DONG X K, LIU T H, CHANG Q, et al. Effects of ethanol Moringa oleifera leaves extract on nonalcoholic fatty liver disease in ZDF rats[J]. Global Traditional Chinese Medicine,2019,12(8):1149−1153. DONG X K, LIU T H, CHANG Q, et al. Effects of ethanol Moringa oleifera leaves extract on nonalcoholic fatty liver disease in ZDF rats[J]. Global Traditional Chinese Medicine, 2019, 12(8): 1149-1153.
[8]	GHASI S, WOBODO E, OFILI J O. Hypocholesterolemic effects of crude extract of leaf of Moringa oleifera Lam in high-fat diet fed wistar rats[J]. Journal of Ethnopharmacology,2000,69(1):21−25. doi: 10.1016/S0378-8741(99)00106-3
[9]	XIE J, WANG Y, JIANG W W, et al. Moringa oleifera leaf petroleum ether extract inhibits lipogenesis by activating the AMPK signaling pathway[J]. Front Pharmacol,2018,9:1447. doi: 10.3389/fphar.2018.01447
[10]	LUO T, LU Y, YAN S, et al. Network pharmacology in research of chinese medicine formula: Methodology, application and prospective[J]. Chinese Journal of Integrative Medicine,2020,26(1):72−80. doi: 10.1007/s11655-019-3064-0
[11]	WANG Y F, XUE H, SUN M X, et al. Prevention and control of obesity in China[J]. The Lancet Global Health,2019,7(9):e1166−e1167. doi: 10.1016/S2214-109X(19)30276-1
[12]	BHASKARAN K, DOUGLAS I, FORBES H, et al. Body-mass index and risk of 22 specific cancers: A population-based cohort study of 5.24 million UK adults[J]. Lancet,2014,384(9945):755−765. doi: 10.1016/S0140-6736(14)60892-8
[13]	ILIAS M, GEORGE S, EFROSYNI P. Hypoxia-inducible factors and the regulation of lipid metabolism[J]. Cells,2019,8(3):214. doi: 10.3390/cells8030214
[14]	WANG Q, WANG S T, YANG X, et al. Myricetin suppresses differentiation of 3T3-L1 preadipocytes and enhances lipolysis in adipocytes[J]. Nutr Res,2015,35(4):317−327. doi: 10.1016/j.nutres.2014.12.009
[15]	魏颖, 张嘉诚, 李晓娟, 等. 基于经典胰岛素传导及炎症信号通路的相互作用中药改善胰岛素抵抗作用研究进展[J]. 世界科学技术-中医药现代化,2022,24(5):2026−2034. [WEI Y, ZHANG J C, LI X J, et al. Research progress of traditional Chinese medicine on alleviating insulin resistance based on classical insulin conduction and inflammatory signal pathway[J]. Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology,2022,24(5):2026−2034. WEI Y, ZHANG J C, LI X J, et al. Research progress of traditional Chinese medicine on alleviating insulin resistance based on classical insulin conduction and inflammatory signal pathway[J]. Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology, 2022, 24(5): 2026-2034.
[16]	王芝. CCDC 86通过正向调控EGFR-PI3K/Akt信号通路促进人鼻咽癌细胞的增殖及侵袭迁移的机制研究[D]. 南昌: 南昌大学, 2021. WANG Z. CCDC 86 promotes the proliferation, invasion and migration of nasopharyngeal carcinoma cells via positively regulating the EGFR-PI3K/Akt signaling[D]. Nanchang: Nanchang University, 2021.
[17]	GUO Y, TAN J, XIONG W, et al. Notch3 promotes 3T3-L1 pre-adipocytes differentiation by up-regulating the expression of LARS to activate the mTOR pathway[J]. Journal of Cellular and Molecular Medicine,2020,24(1):1116−1127. doi: 10.1111/jcmm.14849
[18]	巫亭. 异槲皮苷通过调控miRNA-29a和PI3K/AKT/GSK3β/GLUT4通路改善胰岛素抵抗的研究[D]. 桂林: 桂林医学院, 2019. WU T. Isoquercitrin ameliorates insulin resistance via regulating miR-29a and PI3K/AKT Gsk3β/GLUT4 pathway in HepG2 cells[D]. Guilin: Guilin Medical University, 2019.
[19]	JIAO W Y, MI S, SANG Y X, et al. Integrated network pharmacology and cellular assay for the investigation of an anti-obesity effect of 6-shogaol[J]. Food Chemistry,2022,374:131755−131755.
[20]	LEE H R, KIM D H, KIM M G, et al. The regulation of autophagy in porcine blastocysts: Regulation of PARylation-mediated autophagy via mammalian target of rapamycin complex 1 (mTORC1) signaling[J]. Biochem Biophys Res Commun,2016,473(4):899−906. doi: 10.1016/j.bbrc.2016.03.148
[21]	SAXTON R A, SABATINI D M. mTOR Signaling in growth, metabolism, and disease[J]. Cell,2017,168(6):960−976. doi: 10.1016/j.cell.2017.02.004
[22]	廖媛. 基于MAPK-ERK-TLRs通路探讨脂必泰对非酒精性脂肪性肝病的作用机制及临床疗效研究[D]. 广州: 广州中医药大学, 2020. LIAO Y. Explore the mechanism and clinical efficacy of Zhibitai on NAFLD based on the MAPK-ERK-TLRs pathway[D]. Guangzhou: Guangzhou University of Chinese Medicine, 2020.
[23]	孙大伟. 肝细胞癌一线靶向治疗药物耐药机制及逆转耐药策略研究[D]. 长春: 吉林大学, 2022. SUN D W. The underlying mechanism and overriding methods for first-line targeted drugs resistance in hepatocellular carcinoma[D]. Changchun: Jilin University, 2022.
[24]	HSIN K Y, GHOSH S, KITANO H K. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology[J]. PLoS One,2018,8(12):e83922.
[25]	MEDEIROS D L, LIMA E, SILVE J C, et al. Rhamnetin: A review of its pharmacology and toxicity[J]. J Pharm Pharmacol,2022,74(6):793−799. doi: 10.1093/jpp/rgab163
[26]	JI S Y, CHOI K M, LEE Y S, et al. Rhamnetin-induced suppression of clonal expansion during early stage of adipogenesis[J]. Arch Pharm Res,2012,35(6):1083−1089. doi: 10.1007/s12272-012-0616-7
[27]	JNAWALI H N, LEE E, JEONG K W, et al. Anti-inflammatory activity of rhamnetin and a model of its binding to c-Jun NH2-terminal kinase 1 and p38 MAPK[J]. J Nat Prod,2014,77(2):258−263. doi: 10.1021/np400803n
[28]	HAN M S, JUNG D Y, MOREL C, et al. JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation[J]. Science,2013,339(6116):218−222. doi: 10.1126/science.1227568
[29]	DENG B, SHEN W J, DONG D, et al. Plasma membrane cholesterol trafficking in steroidogenesis[J]. FASEB J,2019,33(1):1389−1400. doi: 10.1096/fj.201800697RRR
[30]	ABUMWEIS S S, MARINANGELI C P, FROHLICH J, et al. Implementing phytosterols into medical practice as a cholesterol-lowering strategy: Overview of efficacy, effectiveness, and safety[J]. Can J Cardiol,2014,30(10):1225−1232. doi: 10.1016/j.cjca.2014.04.022
[31]	ALFREDL W. Chemical and microbiological considerations of phytosterols and their relative efficacies in functional foods for the lowering of serum cholesterol levels in humans: A review[J]. Journal of Functional Foods, 2014, 6.
[32]	JEONG H Y, YUN H J, KIM B W, et al. Widdrol-induced lipolysis is mediated by PKC and MEK/ERK in 3T3-L1 adipocytes[J]. Mol Cell Biochem,2015,410(1-2):247−254. doi: 10.1007/s11010-015-2558-0
[33]	HE K, LI X, XIAO Y, et al. Hypolipidemic effects of Myrica rubra extracts and main compounds in C57BL/6j mice[J]. Food Funct,2016,7(8):3505−3515. doi: 10.1039/C6FO00623J
[34]	XU N, ZHANG L, DONG J, et al. Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice[J]. Molecular Nutrition & Food Research,2014,58(6):1258−1268.
[35]	JIA W, TIAN G, FENG W, et al. Luteolin improves myocardial cell glucolipid metabolism by inhibiting hypoxia inducible factor-1α expression in angiotensin II/hypoxia-induced hypertrophic H9c2 cells[J]. Nutrition Research,2019,65:63−70. doi: 10.1016/j.nutres.2019.02.004
[36]	DING X, ZHENG L, YANG B, et al. Luteolin attenuates atherosclerosis via modulating signal transducer and activator of transcription 3-mediated inflammatory response[J]. Drug Des Devel Ther,2019,13:3899−3911. doi: 10.2147/DDDT.S207185

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