Volume 11,Issue 2
Mechanism of Ilex cornuta Leaves in Diabetes Mellitus and its Cardiovascular Complications: a network pharmacology and molecular docking study
This study employed network pharmacology and molecular docking to investigate the key components and mechanisms of Ilex cornuta leaves (LCL) in treating diabetes mellitus (DM) and its cardiovascular complications. Nine active ingredients—including quercetin, kaempferol and β-sitosterol—were identified via the TCMSP database. Cross-referencing with DM-related targets from GeneCards yielded 144 common targets, of which 16 (notably AKT1, TNF and IL6) were defined as core targets. GO and KEGG analyses indicated that LCL may improve insulin resistance, suppress inflammation and reduce oxidative stress by modulating PI3K-Akt, MAPK and AGE-RAGE signaling. Molecular docking confirmed strong binding of quercetin to all ten top core targets (binding energies < -6.6 kcal/mol). The results reveal a multi-component, multi-target, multi-pathway mode of action and provide a theoretical basis for LCL in treating DM and its cardiovascular complications.
[1] Lovic D, Piperidou A, Zografou I, et al., 2020, The Growing Epidemic of Diabetes Mellitus. Curr Vasc Pharmacol, 18(2): 104-109.
[2] Dal Canto E, Ceriello A, Rydén L, et al., 2019, Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol, 26(2 Suppl): 25-32.
[3] Cole JB, Florez JC, 2020, Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol, 16(7): 377-390.
[4] Betts KA, Song J, Faust E, et al., 2021, Medical costs for managing chronic kidney disease and related complications in patients with chronic kidney disease and type 2 diabetes. Am J Manag Care, 27(20 Suppl): S369-S374.
[5] Saw M, Wong VW, Ho IV, et al., 2019, New anti-hyperglycaemic agents for type 2 diabetes and their effects on diabetic retinopathy. Eye (Lond), 33(12): 1842-1851.
[6] Yang K, Wang Y, Li YW, et al., 2022, Progress in the treatment of diabetic peripheral neuropathy. Biomed Pharmacother, 148: 112717.
[7] Shi L, Fonseca V, Childs B, 2021, Economic burden of diabetes-related hypoglycemia on patients, payors, and employers. J Diabetes Complications, 35(6): 107916.
[8] Yang YF, Yan YN, 2002, Research on the chemical composition of Ilex cornuta leaves. Chinese Journal of Information on Traditional Chinese Medicine, 009(004): 33-34.
[9] Chen X, 2016, Research on Improving the Quality Standard of Ilex cornuta leaves. Southwest Jiaotong University.
[10] Yuan Y, Pan S, Yang SL, et al., 2017, Antioxidant and cardioprotective effects of Ilex cornuta on myocardial ischemia injury. Chin J Nat Med, 15(2): 94-104.
[11] Long H, 2025, Chemical composition and in vitro anti-inflammatory activity screening of Ilex cornuta leaves. Hubei University.
[12] Feng H, Tang J, Zhang P, et al., 2020, Anti-adipogenic 18,19-seco-ursane stereoisomers and oleane-type saponins from Ilex cornuta leaves. Phytochemistry, 175: 112363.
[13] Chen J, 2024, Health-preserving and Hypoglycemic tea: CN201510720306.9 [P]. CN106620409A.
[14] Ru J, Li P, Wang J, et al., 2014, TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform, 6: 13.
[15] Luo J, Chen QX, Li P, et al., 2024, Lobelia chinensis Lour inhibits the progression of hepatocellular carcinoma via the regulation of the PTEN/AKT signaling pathway in vivo and in vitro. J Ethnopharmacol, 318(Pt A): 116886.
[16] Daina A, Michielin O, Zoete V, 2019, SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res, 47(W1): W357-W364.
[17] Bardou P, Mariette J, Escudié F, et al., 2014, jvenn: an interactive Venn diagram viewer. BMC Bioinformatics, 15(1): 293.
[18] Szklarczyk D, Kirsch R, Koutrouli M, et al., 2023, The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res, 51(D1): D638-D646.
[19] Zhou Y, Zhou B, Pache L, et al., 2019, Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun, 10(1): 1523.
[20] Kanehisa M, Sato Y, 2020, KEGG Mapper for inferring cellular functions from protein sequences. Protein Sci, 29(1): 28-35.
[21] Tang D, Chen M, Huang X, et al., 2023, SRplot: A free online platform for data visualization and graphing. PLoS One, 18(11): e0294236.