Abstract
［Objective］ To study the potential targets of hypoglycemic effects of components in Guangdong Finger Citron (GFC ) based on network pharmacology.［Methods］ Genes associated with type 2 diabetes mellitus (T2DM) and hyperglycemia are screened using the TTD,DrugBank,OMIM,and DisGeNET databases.Active components of GFC are collected from literature,and potential targets are predicted using the Swiss database.Based on this,key proteins are then identified through the STRING database,and a "disease -active -component -target -pathway" network was constructed using Cytoscape 3.7.1.Functional annotation is further carried out by performing gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG ) pathway enrichment analyses through the DAVID 6.8 database.Finally,molecular docking of the active components of GFC with key targets was performed using AutoDock Vina.［Results］ Through network pharmacology,a total of 551 relevant targets were identified by intersecting the GFC components with disease targets.A "component -target -disease" network is constructed,and the interactions between disease -related proteins are analyzed.The top 10 引用格式：马文聪，吴宇箫，钟诚，等.基于网络药理学和分子对接探究广佛手成分的降血糖作用机制 ［J］.食品与机械，2025，41（5）：10-18.C itation:MA Wencong,WU Yuxiao,ZHONG Cheng,et al.Exploration on hypoglycemic mechanism of components in Guangdong finger citron based on network pharmacology and molecular docking [J].Food & Machinery,2025,41(5):10-18.|components and targets are ranked based on their Degree values.KEGG pathway enrichment analysis reveals three signaling pathways related to hypoglycemic effects.Two main GFC components associated with hypoglycemic effects are identified:byakangelicol and 6,6',7,7'-tetramethoxy -3,3'-biscoumarin.Three related targets (HSP 90AA1,PIK3CA,and PIK3CD) and associated pathways (PI3K-Akt signaling pathway,insulin resistance,and HIF -1 signaling pathway ) are also identified.Molecular docking of the obtained targets with pathways show that byakangelicol has binding energies of -32.6 and -34.7 kJ/mol with HSP 90AA1 and PIK3CA,respectively,while 6',7,7'-tetramethoxy -3,3'-biscoumarin has binding energies of -35.1 and -37.6 kJ/mol with PIK3CD and PIK3CA,respectively.［Conclusion］ It is speculated that byakangelicol and 6,6',7,7'-tetramethoxy -3,3'-biscoumarin are the main components of GFC for hypoglycemic effects.These components may act by targeting HSP 90AA1,PIK3CA,PIK 3CD,and other targets to regulate biological processes such as the PI 3K-Akt signaling pathway,insulin resistance,and HIF -1 signaling pathway.
Publication Date
6-13-2025
First Page
10
Last Page
18
DOI
10.13652/j.spjx.1003.5788.2024.80880
Recommended Citation
Wencong, MA; Yuxiao, WU; Cheng, ZHONG; and Aimei, ZHOU
(2025)
"Exploration on hypoglycemic mechanism of components in Guangdong finger citron based on network pharmacology and molecular docking,"
Food and Machinery: Vol. 41:
Iss.
5, Article 2.
DOI: 10.13652/j.spjx.1003.5788.2024.80880
Available at:
https://www.ifoodmm.cn/journal/vol41/iss5/2
References
[1] 武建平,李文兰,曲中原,等.基于网络药理学探讨桦褐孔菌降血糖功效成分及作用机制 [J].食品工业科技,2021,42(22):18-29.WU J P,LI W L,QU Z Y,et al.Action mechanism of Inonotus obliquus in the treatment of diabetes and the material basis of pharmacodynamics based on network pharmacology [J].Science and Technology of Food Industry,2021,42(22):18-29.
[2] WANG S N,ZHU F.Antidiabetic dietary materials and animal models [J].Food Research International,2016,85:315-331.
[3] 王贺,王镁.基于调节肠道菌群探讨清热类方治疗糖尿病的研究进展 [J].中国实验方剂学杂志,2021,27(3):238-244.WANG H,WANG M.Research progress on heat-clearing Chinese herbal compounds against diabetes based on regulating |intestinal flora [J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(3):238-244.
[4] 林俊,李萍,陈靠山.近5年多糖抗肿瘤活性研究进展 [J].中国中药杂志,2013,38(8):1 116-1 125.LIN J,LI P,CHEN K S.Advance in studies on anti-tumor activity of polysaccharides in latest five years [J].China Journal of Chinese Materia Medica,2013,38(8):1 116-1 125.
[5] GUARIGUATA L,WHITING D R,HAMBLETON I,et al.Global estimates of diabetes prevalence for 2013 and projections for 2035 [J].Diabetes Research and Clinical Practice,2014,103(2):137-149.
[6] CHATTERJEE S,KHUNTI K,DAVIES M J.Type 2 diabetes[J].American Journal of Plant Sciences,2017,389:2 239-2 251.
[7] 杨柳,郭晋平,吴金华,等.二甲双胍治疗 2型糖尿病合并肺结核的临床效果 [J].中华医院感染学杂志,2024,34(17):2 626-2 630.YANG L,GUO J P,WU J H,et al.Clinical effect of metformin on treatment of type 2 diabetes mellitus patientscomplicated with tuberculosis [J].Chinese Journal of Nosocomiology,2024,34(17):2 626-2 630.
[8] 北京高血压防治协会,中国老年学和老年医学学会,北京市社区卫生协会,等.成人高血压合并 2型糖尿病和血脂异常基层防 治 中 国 专 家 共 识 （2024 年 版 ）[J].中 国 全 科 医 学,2024,27(10):3 453-3 474.Beijing Hypertension Association,China Association of Gerontology and Geriatrics,Beijing Community Health Service Association,et al.Chinese expert consensus on grassroots prevention and treatment of hypertension combined with type 2 diabetes mellitus and dyslipidemia in adults 2024 [J].Chinese General Practice,2024,27(10):3 453-3 474.
[9] 姜健,冯珍凤,胡春平,等.滋膵益肾方治疗 2型糖尿病肾病 Ⅳ期 患 者 蛋 白 尿 的 随 机 对 照 研 究 及 机 制 探 讨 [J].中 医 药 学 报,2023,51(11):75-85.JIANG J,FENG Z F,HU C P,et al.Randomized controlled trial and mechanism study of Zicui Yishen formula in the treatment of proteinuria in patients with stage IV type 2 diabetic nephropathy [J].Acta Chinese Medicine and Pharmacology,2023,51(11):75-85.
[10] ZHANG J K,SUN C D,YAN Y Y,et al.Purification of naringin and neohesperidin from Huyou (Citrus changshanensis ) fruit and their effects on glucose consumption in human HepG 2 cells [J].Food Chemistry,2012,135(3):1 471-1 478.
[11] KIM K N,KO Y J,YANG H M,et al.Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L.var.sarcodactylis ) through blocking JNK,ERK and NF- κB signaling pathways in LPS-activated RAW 264.7 cells [J].Food and Chemical Toxicology,2013,57:126-131.
[12] BERLIOCCHI L,CIOCIARO A,RUSSO R,et al.Toxic profile of bergamot essential oil on survival and proliferation of SH-SY 5Y neuroblastoma cells [J].Food and Chemical Toxicology,2011,49(11):2 780-2 792.
[13] 董文南,李克招,张文婷,等.多糖降血糖作用及其机制研究进展 [J].中国实验方剂学杂志,2019,25(19):219-225.DONG W N,LI K Z,ZHANG W T,et al.Progress in hypoglycemic effect and mechanism of polysaccharides [J].Chinese Journal of Experimental Traditional Medical Formulae,2019,25(19):219-225.
[14] 钟艳梅,田庆龙,肖海文,等.不同产地佛手药材的化学成分比较研究 [J].中南药学,2014,12(1):63-66.ZHONG Y M,TIAN Q L,XIAO H W,et al.Chemical constituents of Fructus citri sarcodactylis from different places[J].Central South Pharmacy,2014,12(1):63-66.
[15] 肖 培 根.新 编 中 药 志 [M].北 京:化 学 工 业 出 版 社,2007:10-55.XIAO P G.Modern Chinese materia medica [M].Beijing:Chemical Industry Press,2007:10-55.
[16] 国 家 中 医 药 管 理 局 《中 华 本 草 》编 委 会.中 华 本 草:第4册[M].上海:上海科学技术出版社,1999:911.The Editorial Board of Compendium of Materia Medica (Chinese ) under the State Administration of Traditional Chinese Medicine.Compendium of materia medica (Chinese ):volume 4[M].Shanghai:Shanghai Scientific & Technical Publishers,1999:911.
[17] 张爵玉,蒋林,王琴.广佛手的研究现状及进展 [J].中国调味品,2008 (3):34-36.ZHANG J Y,JIANG L,WANG Q.Advances in studies on bergamot [J].China Condiment,2008 (3):34-36.
[18] 王淑惠.佛手多糖分离纯化与结构鉴定及体外免疫活性和产品开发研究 [D].广州:华南农业大学,2020:67-69.WANG S F.Isolation,purification,structural characterization,in vitro immunostimulatory activity and product development of polysaccharide from bergamot (Citrus medica L.var.sarcodactylis Swingle ) [D].Guangzhou:South China Agricultural University,2022:67-69.
[19] 杨玉洁,刘焕,王淑惠,等.基于酶活力和细胞模型分析广佛手 多 糖 降 血 糖 活 性 及 作 用 机 制 [J].食 品 科 学,2022,43(23):149-157.YANG Y J,LIU H,WANG S H,et al.Hypoglycemic effect and mechanism of polysaccharides from finger citron from Guangdong province based on enzyme activities and cell model [J].Food Science,2022,43(23):149-157.
[20] 周龙艳,田奥飞,胡旭光.佛手化学成分及调节糖脂代谢紊乱药理作用研究进展 [J].广东化工,2017,44(7):146-148.ZHOU L Y,TIAN A F,HU X G.Pharmacological study on glucose and lipid metabolism and regulation of the chemical composition of bergamot [J].Guangdong Chemical Industry,2017,44(7):146-148.
[21] HOPKINS A L.Network pharmacology [J].Nat Biotech,2007,25(10):1 110-1 111.
[22] HOPKINS A L.Network pharmacology:the next paradigm in drug discovery [J].Nature Biotechnology,2008,4(11):682-690.
[23] PEREIRA F,AIRES-DE-SOUSA J.Computational methodologies in the exploaration of marine natural product leads [J].Marine Drugs,2018,16(7):e373.
[24] 朱 菲,吴 梅,孔 向 军,等.金 线 莲 干 预 2型 糖 尿 病 的 “关 键 成分-潜在靶标 -核心通路 ”网络挖掘及实验验证 [J].中草药,2022,53(12):3 720-3 729.ZHU F,WU M,KONG X J,et al.Network mining and experimental verification of "key components-potential targets-core pathways" of Anoectochilus roxburghii in intervention of type 2 diabetic mellitus [J].Chinese Traditional and Herbal Drugs,2022,53(12):3 720-3 729.
[25] SHANNON P,MARKIEL A,OZIER O,et al.Cytoscape:a software environment for integrated models of biomolecular interaction networks [J].Genome Research,2003,13(11):2 498-2 504.
[26] 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 Research,2017,45:D362-D368.
[27] 李小凤,蔡春,程荷凤,等.广佛手多糖的分离纯化与相关成分 的 气 相 色 谱 分 析 [J].广 东 医 学 院 学 报,2005 (3):240-241,259.LI X F,CAI C,CHENG H F,et al.Isolation and purification of polysaccharide from fructus of Citri medica and analysis of its chemical composition by gas chromatography [J].Journal of Guangdong Medical College,2005 (3):240-241,259.
[28] 何 海 音,凌 罗 庆,史 国 萍,等.中 药 广 佛 手 的 化 学 成 分 研 究[J].中药通报,1988 (6):32-34.HE H Y,LING L Q,SHI G P,et al.Study on the chemical constituents of Guangfoshou (Citrus medica var.sarcodactylis ),a traditional Chinese medicine [J].China Journal of Chinese Materia Medica,1988 (6):32-34.
[29] 钟艳梅,冯毅凡,郭姣.基于 UPLC-Q-TOF-MS 的广佛手化学成 分 快 速 鉴 定 研 究 [J].天 然 产 物 研 究 与 开 发,2014,26(12):1 965-1 970,2 040.ZHONG Y M,FENG Y F,GUO J.Rapid identification of components from fructus citri sarcodactylis based on ultra-high performance liquid chromatography time-of-flight mass spectrometry [J].Natural Product Research and Development,2014,26(12):1 965-1 970,2 040.
[30] 吴学峰,周熙,黄晓兰,等.基于 UPLC-Q-TOF-MS 的广佛手指纹图谱建立及炮制前后成分差异分析 [J].分析测试学报,2022,41(3):299-308.WU X F,ZHOU X,HUANG X L,et al.Construction of UPLC-Q-TOF-MS fingerprints for fingered citron and its ingredient differences analysis before and after processing [J].Journal of Instrumental Analysis,2022,41(3):299-308.
[31] 尹锋,楼凤昌.佛手化学成分的研究 [J].中国药学杂志,2004(1):20-21.YIN F,LOU F C.Studies on the constituents of Citrus medica L.·var.sarcodactylis [J].Chinese Pharmaceutical Journal,2004(1):20-21.[32] 尹 锋,成 亮,楼 凤 昌.佛 手 化 学 成 分 的 研 究 [J].中 国 天 然 药物,2004 (3):149-151.YIN F,CHENG L,LOU F C.Studies on the constituents of Citrus medica L.var.sarcodactylis (Noot.) swingle [J].Chinese Journal of Natural Medicines,2004 (3):149-151.
[33] 曾美玲,李朝阳,胡乔,等.基于生物信息学和体外实验探讨金 钗 石 斛 治 疗 2型 糖 尿 病 的 药 理 机 制 [J].中 国 医 院 药 学 杂志,2024,44(14):1 627-1 634.ZENG M L,LI C Y,HU Q,et al.Pharmacological mechanism of Dendrobium nobile for type 2 diabetes mellitus by bioinformatics and in vitro experiment [J].Chinese Journal of Hospital Pharmacy,2024,44(14):1 627-1 634.
[34] 林玉玲,李玉杰,李增一,等.柴胡皂苷 A调控 PI3K/Akt 通路对2型 糖 尿 病 小 鼠 胰 岛 素 抵 抗 的 影 响 [J].中 国 老 年 学 杂 志,2024,44(4):928-931.LIN Y L,LI Y J,LI Z Y,et al.The effect of saikosaponin A in regulating the PI 3K/Akt pathway on insulin resistance in type 2 diabetic mice [J].Chinese Journal of Gerontology,2024,44(4):928-931.
[35] 卢韵宇.PI3K/AKT/mTOR 信号通路调控 HIF- 1α参与弓形虫感染小鼠脾脏糖代谢的研究 [D].南宁:广西医科大学,2021:50-62.LU Y Y.PI3K/AKT/mTOR signaling pathway regulates HIF-1α to participate in the glucose metabolism in the spleen of mice infected with Toxoplasma gondii [D].Nanning:Guangxi Medical University,2021:50-62.
[36] 王琨,杨传华,杨洁.基于网络药理学及分子对接探讨益气活 血 方 治 疗 冠 心 病 的 作 用 机 制 [J].中 西 医 结 合 心 脑 血 管 病杂志,2024,22(13):2 312-2 321.WANG K,YANG C Y,YANG J.The mechanism of Yiqi huoxue formula for treating coronary heart disease based on network pharmacology and molecular docking [J].Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease,2024,22(13):2 312-2 321.
[37] 姚元发.香豆素类化合物对小鼠 2型糖尿病的干预作用及机制研究 [D].杭州:浙江工业大学,2017:44-45.YAO Y F.Study on intervention effects and mechanisms of coumarins on type 2 diabetes in mice [D].Hangzhou:College of Pharmaceutical Sciences Zhejiang University of Technology,2017:44-45.
[38] 潘琳琳,相宏杰,逯艳婷,等.理脾降浊方治疗 2型糖尿病的网 络 药 理 学 和 蛋 白 质 组 学 研 究 [J].世 界 中 医 药,2024,19(12):1 708-1 719.PAN L L,XIANG H J,LU Y T,et al.Network pharmacology and proteomics reveal the mechanism of Lipi Jiangzhuo formula in treating type 2 diabetes mellitus [J].World Chinese Medicine,2024,19(12):1 708-1 719.
[39] LIU M,WANG X Y,YANG J S,et al.Integrated investigation and discovery of therapeutic targets for 3-hydroxybakuchiol against diabetes based on molecular docking studies and cell experiments [J].BMC Complementary Medicine and Therapies,2023,23(1):431.