食品与发酵工业 >

2024 , Vol. 50 >Issue 14: 69 - 77

DOI: https://doi.org/10.13995/j.cnki.11-1802/ts.036272

研究报告

基于网络药理学及分子对接揭示芦荟大黄素的降糖机制

  • 潘若瑶 ,
  • 任国艳 ,
  • 马富利
展开
  • 1(河南科技大学 食品与生物工程学院,河南 洛阳,471000)
    2(河南省食品原料工程研究中心,河南 洛阳,471000)
    3(国家实验食品加工与安全教育示范中心,河南 洛阳,471000)
第一作者：硕士研究生(任国艳教授为通信作者,E-mail:renguoyan@163.com)

收稿日期: 2023-05-28

  修回日期: 2023-07-13

  网络出版日期: 2024-08-02

基金资助

中国国家重点研究发展计划(2018YFD0901102);河南省重点科技攻关项目(182102110345)

收起

Network pharmacology and molecular docking reveal hypoglycemic mechanism of aloe-emodin

  • PAN Ruoyao ,
  • REN Guoyan ,
  • MA Fuli
Expand
  • 1(College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China)
    2(Henan Engineering Research Center of Food Material, Luoyang 471000, China)
    3(National Demonstration Center for Experimental Food Processing and Safety Education, Luoyang 471000, China)

Received date: 2023-05-28

  Revised date: 2023-07-13

  Online published: 2024-08-02

Fold

摘要

该文通过网络药理学结合分子对接的技术研究了芦荟大黄素改善Ⅱ型糖尿病的作用机制。利用数据库平台筛选出芦荟大黄素的潜在靶点和改善治疗Ⅱ型糖尿病的相关靶点,将二者取交集获得芦荟大黄素改善Ⅱ型糖尿病的潜在靶点;构建共同靶点间的蛋白互作网络,并对共同靶点进行GO功能注释和KEGG通路富集分析;通过筛选主要通路并构建“芦荟大黄素-Ⅱ型糖尿病-通路”网络图,对芦荟大黄素与通路及各通路所富集的靶点间的联系进行可视化分析,通过分子对接,研究芦荟大黄素与关键靶点的结合机制。结果表明,芦荟大黄素具有63个改善治疗Ⅱ型糖尿病的相关靶点,并根据蛋白互作网络筛选出AKT1、PIK3CA、HRAS和MAPK8等22个核心靶点,这些靶点主要富集在PI3K/AKT和胰岛素抵抗等信号通路,芦荟大黄素主要通过氢键、范德华力和π-π相互作用等分子间作用力与靶点结合,从而调控靶点的表达,改善Ⅱ型糖尿病。

关键词： 芦荟大黄素; Ⅱ型糖尿病; 网络药理学; 分子对接

本文引用格式

潘若瑶 , 任国艳 , 马富利 . 基于网络药理学及分子对接揭示芦荟大黄素的降糖机制[J]. 食品与发酵工业, 2024 , 50(14) : 69 -77 . DOI: 10.13995/j.cnki.11-1802/ts.036272

Abstract

The mechanism of action of aloe-emodin for improving type Ⅱ diabetes was investigated by network pharmacology combined with molecular docking technique.The potential targets of aloe-emodin and the related targets for improving the treatment of type Ⅱ diabetes were screened by using the database platform, and the potential targets of aloe-emodin for improving type Ⅱ diabetes were obtained by intersecting the two.The protein interaction network between the common targets was constructed, and the GO function annotation and KEGG pathway enrichment analysis were performed for the common targets.By screening the main pathways and constructing a network diagram of “aloe-emodin-type Ⅱ diabetes-pathway”, this study visualized the linkage between aloe emodin and the pathways and the targets enriched by each pathway and studied the binding mechanism between aloe-emodin and the key targets through molecular docking.Results showed that aloe-emodin had 63 targets for improving the treatment of type Ⅱ diabetes, and 22 core targets, including AKT1, PIK3CA, HRAS, and MAPK8, were identified based on the protein interaction network, which was mainly enriched in PI3K/AKT and insulin resistance signaling pathways.Aloe-emodin bound to the targets mainly through intermolecular forces such as hydrogen bonding, van der Waals forces, and π-π interactions, thus regulating the expression of the targets and improving type Ⅱ diabetes.

Key words： aloe-emodin; type 2 diabetes; network pharmacology; molecular docking

参考文献

[1] NAEMI R, SHAHMORADI L.Global experience of diabetes registries:A systematic review[J].Advances in Experimental Medicine and Biology, 2021, 1307:441-455.
[2] 杨玉洁, 刘静宜, 谭艳, 等.多糖降血糖活性构效关系及作用机制研究进展[J].食品科学, 2021, 42(23):355-363.
YANG Y J, LIU J Y, TAN Y, et al.Progress in understanding the structure-activity relationship and hypoglycemic mechanism of polysaccharides[J].Food Science, 2021, 42(23):355-363.
[3] GRUNBERGER G.Should side effects influence the selection of antidiabetic therapies in type 2 diabetes?[J].Current Diabetes Reports, 2017, 17(4):21.
[4] XIAN M H, CAI J L, ZHENG K N, et al.Aloe-emodin prevents nerve injury and neuroinflammation caused by ischemic stroke via the PI3K/AKT/mTOR and NF-κB pathway[J].Food and Function, 2021, 12(17):8056-8067.
[5] ABDELLATEF A A, FATHY M, MOHAMMED A E S I, et al.Inhibition of cell-intrinsic NF-κB activity and metastatic abilities of breast cancer by aloe-emodin and emodic-acid isolated from Asphodelus microcarpus[J].Journal of Natural Medicines, 2021, 75(4):840-853.
[6] PÉREZ Y Y, JIMÉNEZ-FERRER E, ZAMILPA A, et al.Effect of a polyphenol-rich extract from aloe vera gel on experimentally induced insulin resistance in mice[J].The American Journal of Chinese Medicine, 2007, 35(6):1037-1046.
[7] 丁浩轩, 赵阳, 冯杰.基于网络药理学探讨植物提取物在饲料添加剂领域的研究进展[J].动物营养学报, 2021, 33(6):3065-3071.
DING H X, ZHAO Y, FENG J.Research progress on discussion of plant extracts in field of feed additives based on network pharmacology[J].Chinese Journal of Animal Nutrition, 2021, 33(6):3065-3071.
[8] 赵梦瑶, 潘芊钰, 曹颖.基于网络药理学探究金芪降糖片治疗2型糖尿病作用机制[J].中国医药科学, 2023, 13(5):45-48;56.
ZHAO M Y, PAN Q Y, CAO Y.Exploring the mechanism of jinqi Jiangtang Tablets in the treatment of type 2 diabetes mellitus based on network pharmacology[J].China Medicine, 2023, 13(5):45-48;56.
[9] 黄慧珍, 王松松, 林凡, 等.基于网络药理学探讨石斛治疗2型糖尿病的作用机制[J].世界中医药, 2022, 17(19):2718-2722.
HUANG H Z, WANG S S, LIN F, et al.Mechanism of dendrobii caulis in treatment of type 2 diabetes based on network pharmacology[J].World Chinese Medicine, 2022, 17(19):2718-2722.
[10] SZKLARCZYK D, GABLE A L, LYON D, et al.STRING v11:Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J].Nucleic Acids Research, 2018, 47(D1):D607-D613.
[11] ZHENG S C, BAAK J P, LI S, et al.Network pharmacology analysis of the therapeutic mechanisms of the traditional Chinese herbal formula Lian Hua Qing Wen in Corona virus disease 2019 (COVID-19), gives fundamental support to the clinical use of LHQW[J].Phytomedicine, 2020, 79:153336.
[12] 李佳芸, 王欣之, 韦源青, 等.基于网络药理学与分子对接研究马氏珍珠贝降糖活性肽[J].食品与发酵工业, 2022, 48(15):176-184.
LI J Y, WANG X Z, WEI Y Q, et al.Screening of potential anti-diabetic peptides from Pinctada martensii flesh based on network pharmacology and molecular docking techniques[J].Food and Fermentation Industries, 2022, 48(15):176-184.
[13] 董硕, 汤春波.PI3K/AKT信号通路在2型糖尿病患者种植体骨结合中作用机制的研究进展[J].口腔医学, 2022, 42(11):1026-1030;1035.
DONG S, TANG C B.Progress of research on the mechanism of PI3K/AKT signaling pathway in implant osseointegration in patients with type 2 diabetes mellitus[J].Stomatology, 2022, 42(11):1026-1030;1035.
[14] TOMITA T.Apoptosis in pancreatic β-islet cells in type 2 diabetes[J].Bosnian Journal of Basic Medical Sciences, 2016, 16(3):162-179.
[15] JUD P, SOURIJ H.Therapeutic options to reduce advanced glycation end products in patients with diabetes mellitus:A review[J].Diabetes Research and Clinical Practice, 2019, 148:54-63.
[16] HAYES H L, PETERSON B S, HALDEMAN J M, et al.Delayed apoptosis allows islet β-cells to implement an autophagic mechanism to promote cell survival[J].PLoS One, 2017, 12(2):e0172567.
[17] MIETTINEN P J, HUOTARI M A, KOIVISTO T, et al.Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors[J].Development, 2000, 127(12):2617-2627.
[18] MEIER D T, TU L H, ZRAIKA S, et al.Matrix metalloproteinase-9 protects islets from amyloid-induced toxicity[J].The Journal of Biological Chemistry, 2015, 290(51):30475-30485.
[19] NAGY V, BOZDAGI O, MATYNIA A, et al.Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory[J].The Journal of Neuroscience, 2006, 26(7):1923-1934.
[20] WAGMAN A S, JOHNSON K W, BUSSIERE D E.Discovery and development of GSK3 inhibitors for the treatment of type 2 diabetes[J].Current Pharmaceutical Design, 2004, 10(10):1105-1137.
[21] BADER G D, BETEL D, HOGUE C W V.BIND:The biomolecular interaction network database[J].Nucleic Acids Research, 2003, 31(1):248-250.
[22] BELLINGER D A, MERRICKS E P, NICHOLS T C.Swine models of type 2 diabetes mellitus:Insulin resistance, glucose tolerance, and cardiovascular complications[J].ILAR Journal, 2006, 47(3):243-258.
[23] SIGISMUND S, AVANZATO D, LANZETTI L.Emerging functions of the EGFR in cancer[J].Molecular Oncology, 2018, 12(1):3-20.
[24] LI Z L, LI Y, OVERSTREET J M, et al.Inhibition of epidermal growth factor receptor activation is associated with improved diabetic nephropathy and insulin resistance in type 2 diabetes[J].Diabetes, 2018, 67(9):1847-1857.
[25] LAMBADIARI V, MITROU P, MARATOU E, et al.Thyroid hormones are positively associated with insulin resistance early in the development of type 2 diabetes[J].Endocrine, 2011, 39(1):28-32.
[26] AL-KURAISHY H M, AL-GAREEB A I, AWAD M S, et al.Assessment of serum prolactin levels in acute myocardial infarction:The role of pharmacotherapy[J].Indian Journal of Endocrinology and Metabolism, 2016, 20(1):72-79.
[27] RASHEED H A, AL-KURAISHY H M, AL-GAREEB A I, et al.Effects of diabetic pharmacotherapy on prolactin hormone in patients with type 2 diabetes mellitus:Bane or boon[J].Journal of Advanced Pharmaceutical Technology & Research, 2019, 10(4):163-168.
[28] TIWARI A, AL-ROBEH H, SHARMA H, et al.Steroid-induced diabetic ketoacidosis in a patient with type 2 diabetes mellitus[J].AACE Clinical Case Reports, 2018, 4(2):131-133.
[29] SHAH P, KALRA S, YADAV Y, et al.Management of glucocorticoid-induced hyperglycemia[J].Diabetes, Metabolic Syndrome and Obesity:Targets and Therapy, 2022, 15:1577-1588.
[30] CLORE J N, THURBY-HAY L.Glucocorticoid-induced hyperglycemia[J].Endocrine Practice: Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2009, 15(5):469-474.
[31] LE T N, NESTLER J E, STRAUSS J F, et al.Sex hormone-binding globulin and type 2 diabetes mellitus[J].Trends in Endocrinology and Metabolism, 2012, 23(1):32-40.
[32] ELKSNIS A, MARTINELL M, ERIKSSON O, et al.Heterogeneity of metabolic defects in type 2 diabetes and its relation to reactive oxygen species and alterations in beta-cell mass[J].Frontiers in Physiology, 2019, 10:107.
[33] KHONDKARYAN L, MARGARYAN S, POGHOSYAN D, et al.Impaired inflammatory response to LPS in type 2 diabetes mellitus[J].International Journal of Inflammation, 2018, 2018:2157434.
[34] GAO J R, QIN X J, FANG Z H, et al.To explore the pathogenesis of vascular lesion of type 2 diabetes mellitus based on the PI3K/Akt signaling pathway[J].Journal of Diabetes Research, 2019, 2019:4650906.
[35] HUANG X J, LIU G H, GUO J, et al.The PI3K/AKT pathway in obesity and type 2 diabetes[J].International Journal of Biological Sciences, 2018, 14(11):1483-1496.
[36] ABDEL-MONEIM A, BAKERY H H, ALLAM G.The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus[J].Biomedicine and Pharmacotherapy, 2018, 101:287-292.
[37] YOON M S.The role of mammalian target of rapamycin (mTOR) in insulin signaling[J].Nutrients, 2017, 9(11):1176.
[38] CUI W, XU B, CHEN F, et al. Effects of grape peel phenolics on lipid accumulation in sodium palmitate-treated HepG2 cells. Journal of Functional Foods, 2024, 112: 105923.
Options
文章导航

/

〈 〉

技术支持：北京玛格泰克科技发展有限公司