To study the anti-atherosclerosis mechanism of action of peanut skin polyphenols, network pharmacology and molecular docking techniques were used to predict the active components, targets, and pathways. The active components of peanut skin polyphenols were obtained through the TCMSP platform and literature search, and the related targets of peanut skin polyphenols and atherosclerosis were obtained by using the relevant databases. GO and KEGG enrichment analyses were performed by the DAVID database. The “active components of peanut skin polyphenols-target-pathway” interaction network was constructed by Cytoscape software. Finally, molecular docking of active ingredients and the core target were performed using AutoDockTools software. Results showed that 13 active components of peanut skin polyphenols such as kaempferol, epicatechin, fisetin, catechin, luteolin, quercetin, procyanidin B1, and epigallocatechin gallate were screened. And 65 key targets such as alpha serine/threonine-protein kinase (AKT1), phosphatidylinositol 3-kinase regulatory subunit 1 (PIK3R1), mitogen-activated protein kinase-1 (MAPK1), epithelial growth factor receptor (EGFR), and tumor protein p53(TP53) were obtained. The peanut skin polyphenols played an anti-atherosclerosis effect, mainly involving the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, lipid and atherosclerosis, fluid shear stress and atherosclerosis, interleukin-17 (IL-17) signaling pathway, and EGFR tyrosine kinase inhibitor resistance. The results of molecular docking showed that the main active components could be stably combined with key targets. Peanut skin polyphenols could against atherosclerosis through collaborative intervention in physiological processes through multiple components, multiple targets, and multiple pathways. The physiological processes mainly included lipid metabolism, inflammation, and cell proliferation and apoptosis. The result provided a theoretical basis for the development of anti-atherosclerosis functional food with peanut skin.
[1] 高锦鸿, 芦鑫, 孙强, 等.不同品种花生红衣中八种酚类物质成分分析[J].食品与发酵工业, 2022,48(14):218-225.
GAO J H, LU X, SUN Q, et al.Analysis of eight phenolic contents in peanuts skin from different cultivars[J].Food and Fermentation Industries, 2022,48(14):218-225.
[2] YU J M, AHMEDNA M, GOKTEPE I.Effects of processing methods and extraction solvents on concentration and antioxidant activity of peanut skin phenolics[J].Food Chemistry, 2005,90(1-2):199-206.
[3] MA Y Y, KOSIŃSKA-CAGNAZZO A, KERR W L, et al.Separation and characterization of phenolic compounds from dry-blanched peanut skins by liquid chromatography-electrospray ionization mass spectrometry[J].Journal of Chromatography A, 2014,1356:64-81.
[4] BODOIRA R, CECILIA CITTADINI M, VELEZ A, et al.An overview on extraction, composition, bioactivity and food applications of peanut phenolics[J].Food Chemistry, 2022,381:132250.
[5] AHMADI A, JAMIALAHMADI T, SAHEBKAR A.Polyphenols and atherosclerosis:A critical review of clinical effects on LDL oxidation[J].Pharmacological Research, 2022,184:106414.
[6] CHENG X B, ZHAO C L, JIN Z W, et al.Natural products:potential therapeutic agents for atherosclerosis[J].Chinese Journal of Natural Medicines, 2022,20(11):830-845.
[7] LU X L, ZHAO C H, YAO X L, et al.Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway[J].Biomedicine & Pharmacotherapy, 2017,85:658-671.
[8] MORRISON M, VAN DER HEIJDEN R, HEERINGA P, et al.Epicatechin attenuates atherosclerosis and exerts anti-inflammatory effects on diet-induced human-CRP and NFκB in vivo[J].Atherosclerosis, 2014,233(1):149-156.
[9] TOOMER O T, VU T, PEREIRA M, et al.Dietary supplementation with peanut skin polyphenolic extracts (PSPE) reduces hepatic lipid and glycogen stores in mice fed an atherogenic diet[J].Journal of Functional Foods, 2019,55:362-370.
[10] XU M J, LV C, WANG H X, et al.Peanut skin extract ameliorates high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and gut microbiota in ApoE-/-mice[J].Food Research International, 2022,154:111014.
[11] 王腾飞, 段瑞斌, 杨佳丽, 等.基于网络药理学和分子对接探讨毛建茶干预高脂血症的作用机制[J].食品科学, 2023,44(9):7-14.
WANG T F, DUAN R B, YANG J L, et al.Using network pharmacology and molecular docking to explore the mechanism by which Dracocephalum rupestre hance tea intervenes in hyperlipidemia. Food Science, 2023, 44(9):7-14.
[12] 杨娟, 豆佳红, 孙悦龙, 等.基于网络药理学与分子对接和实验验证探讨费菜抗炎作用的分子机制[J].食品工业科技, 2023, 44(4):12-21.
YANG J, DOU J H, SUN Y L, et al.Molecular mechanism of Phedimus aizoon (Linnaeus)’t hart.on anti-inflammatory effect based on network pharmacology and molecular docking and experiment research[J].Science and Technology of Food Industry, 2023, 44(4):12-21.
[13] BI Y M, HAN X, LAI Y G, et al.Systems pharmacological study based on UHPLC-Q-Orbitrap-HRMS, network pharmacology and experimental validation to explore the potential mechanisms of Danggui-Shaoyao-San against atherosclerosis[J].Journal of Ethnopharmacology, 2021,278:114278.
[14] DUAN H, KHAN G J, SHANG L J, et al.Computational pharmacology and bioinformatics to explore the potential mechanism of Schisandra against atherosclerosis[J].Food and Chemical Toxicology, 2021,150:112058.
[15] ZHANG B C, LI Z, XU W, et al.Luteolin alleviates NLRP3 inflammasome activation and directs macrophage polarization in lipopolysaccharide-stimulated RAW264.7 cells[J].American Journal of Translational Research, 2018,10(1):265-273.
[16] 张宸豪, 李瑶, 李正祎, 等.原花青素B1对LPS诱导小鼠巨噬细胞RAW264.7损伤的保护作用及其机制[J].吉林大学学报(医学版), 2019,45(6):1243-1247;1481.
ZHANG C H, LI Y, LI Z Y, et al.Protective effect of procyanidine B1 on LPS-induced injury of mouse macrophages RAW264.7 and its mechanism[J].Journal of Jilin University(Medicine Edition), 2019,45(6):1243-1247;1481.
[17] WANG L T, HUANG Z Q, HUANG W J, et al.Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress[J].Scientific Reports, 2017,7:45917.
[18] ZEBOUDJ L, GIRAUD A, GUYONNET L, et al.Selective EGFR (epidermal growth factor receptor) deletion in myeloid cells limits atherosclerosis—brief report[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2018,38(1):114-119.
[19] SIMO-CHEYOU E R, VARDATSIKOS G, SRIVASTAVA A K.Src tyrosine kinase mediates endothelin-1-induced early growth response protein-1 expression via MAP kinase-dependent pathways in vascular smooth muscle cells[J].International Journal of Molecular Medicine, 2016,38(6):1879-1886.
[20] TAO H, YANCEY P G, BABAEV V R, et al.Macrophage SR-BI mediates efferocytosis via Src/PI3K/Rac1 signaling and reduces atherosclerotic lesion necrosis[J].Journal of Lipid Research, 2015,56(8):1449-1460.
[21] ABEYRATHNA P, SU Y C.The critical role of Akt in cardiovascular function[J].Vascular Pharmacology, 2015,74:38-48.
[22] ZHANG T Y, HUANG J T, YI Y Q, et al.Akt serine/threonine kinase 1 regulatede Novo fatty acid synthesis through the mammalian target of rapamycin/sterol regulatory element binding protein 1 axis in dairy goat mammary epithelial cells[J].Journal of Agricultural and Food Chemistry, 2018,66(5):1197-1205.
[23] REN Q, GUO F, TAO S B, et al.Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice[J].Biomedicine & Pharmacotherapy, 2020,122:109772.
[24] XU T, WANG Q G, LIU M.A network pharmacology approach to explore the potential mechanisms of huangqin-baishao herb pair in treatment of cancer[J].Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2020,26:e923199.
[25] VALTER L, MORENA G, RITA P M, et al.Relationship among IL-6, LDL cholesterol and lipid peroxidation[J].Cellular and Molecular Biology Letters, 2015,20(2):310-322.
[26] ZHOU C Y, CHEN J, ZHANG H Z, et al.Investigation of the chemical profile and anti-inflammatory mechanisms of flavonoids from Artemisia vestita Wall.ex Besser via targeted metabolomics, zebrafish model, and network pharmacology[J].Journal of Ethnopharmacology, 2023,302:115932.
[27] KIM J, JANG S, PARK E, et al.The role of heat shock protein 90 in migration and proliferation of vascular smooth muscle cells in the development of atherosclerosis[J].Journal of Molecular and Cellular Cardiology, 2014,72:157-167.
[28] NAKAYAMA A, ALBARRÁN-JUÁREZ J, LIANG G Z, et al.Disturbed flow-induced Gs-mediated signaling protects against endothelial inflammation and atherosclerosis[J].JCI Insight, 2020,5(23):e140485.
[29] ZHOU J, LI Y S, CHIEN S.Shear stress-initiated signaling and its regulation of endothelial function[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2014,34(10):2191-2198.
[30] MOEINAFSHAR A, RAZI S, REZAEI N.Interleukin 17, the double-edged sword in atherosclerosis[J].Immunobiology, 2022,227(3):152220.
