Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (11): 70-81.doi: 10.6040/j.issn.1671-7554.0.2022.0911

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Network pharmacologic mechanism of Huangqi Guizhi Wuwu Decoction in treating heart failure

FAN Xiaoyan1, WANG Yuangeng2, CHEN Zetao3   

  1. 1. The First Department of Cardiovascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China;
    2. First Clinical College of Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China;
    3. Geriatrics Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China
  • Online:2022-11-10 Published:2022-11-04

Abstract: Objective To explore the mechanism of action of Huangqi Guizhi Wuwu Decoction(the Decoction)in the treatment of heart failure by using network pharmacology-molecular docking technique. Methods The drug components of the Decoction were obtained from the TCMSP database, the targets of drug components were obtained from the Uniprot database, the targets of heart failure were obtained from the GeneCard, OMIM, pharmgkb, TTD, DrugBank databases, and the common targets of the Decoction and heart failure were analyzed with R software. Protein-protein interaction(PPI), gene ontology(GO), Kyoto encyclopedia of genes and genomes(KEGG), and molecular docking analyses were performed using R, Cytoscape, Autodock, and pymol softwares. Results A total of 84 targets of the Decoction, 1,430 differential genes of heart failure, and 118 common targets were obtained. Pathway enrichment analysis of common targets showed that they were mainly related to mitogen activated protein kinase(MAPK)and interleukin-17(IL-17). The results of molecular docking showed that the core target of heart failure had good affinity with the main components of the Decoction, which could bind freely and effectively. Conclusion Quercetin, isorhamnetin and formononetin in the Decoction can play a role in the treatment of heart failure through anti-oxidative stress and anti-fibrosis. The Decoction has multi-level, multi-channel and multi-target effects on heart failure.

Key words: Heart failure, Huangqi Guizhi Wuwu Decoction, Network pharmacology, Molecular docking

CLC Number: 

  • R681.5
[1] 王华,梁延春.中国心力衰竭诊断和治疗指南2018[J].中华心血管病杂志, 2018, 46(10): 760-789.
[2] McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure [J]. Eur Heart J, 2021, 42(36): 3599-3726.
[3] 李星星. 益气活血利水方改善冠心病慢性心衰患者心功能及生存质量的研究[D]. 北京:北京中医药大学, 2020.
[4] 孙碧鸿. 补阳还五汤化裁对慢性心力衰竭患者生存质量及预后的影响[D]. 哈尔滨:黑龙江中医药大学, 2020.
[5] 张裕珍, 姚娜. 黄芪桂枝五物汤治疗急性心肌梗死临床观察[J]. 光明中医, 2021, 36(22): 3832-3834. ZHANG Yuzhen, YAO Na. Clinical observation on Huangqi Guizhi Wuwu Decoction on acute myocardial infarction [J]. Guangming Journal of Chinese Medicine, 2021, 36(22): 3832-3834.
[6] 沈中琪, 黎丽娴, 谭景光, 等. 黄芪桂枝五物汤治疗气虚血瘀型慢性心力衰竭运动耐量的临床观察[J]. 云南中医中药杂志, 2019, 40(5): 54-56. SHEN Zhongqi, LI Lixian, TAN Jingguang, et al. Clinical observation on Huangqi Guizhi Wuwu Decoction in treating exercise tolerance of chronic heart failure caused by qi deficiency and blood stasis [J]. Yunnan Journal of Traditional Chinese Medicine and Materia Medica, 2019, 40(5): 54-56.
[7] 张润萍, 胡明丽. 黄芪桂枝五物合真武汤加减治疗慢性心力衰竭临床观察[J]. 光明中医, 2021, 36(8): 1224-1226. ZHANG Runping, HU Mingli. Observation on the curative effect of Huangqi Guizhi Wuwu Decoction and Zhenwu Decoction in the treatment of chronic heart failure [J]. Guangming Journal of Chinese Medicine, 2021, 36(8): 1224-1226.
[8] 黄圣, 弓航, 赵乐滢, 等. 基于网络药理学和分子对接技术探究生脉注射液对急性心肌梗死与短暂性脑缺血发作异病同治的机制[J]. 中国药师, 2021, 24(10): 1838-1846. HUANG Sheng, GONG Hang, ZHAO Leying, et al. Exploration of the same treatment for different diseases mechanism of Shengmai injection in treating acute myocardial infarction and transient ischemia attack based on network pharmacology and molecu-lar docking technology [J]. Transactions of Nonferrous Metals Society of China, 2021, 24(10): 1838-1846.
[9] 蔡萧君, 王磊, 江柏华, 等. 基于液相色谱-四极杆/飞行时间质谱血液代谢组学的黄芪桂枝五物汤干预血瘀证大鼠的研究[J]. 中国医院用药评价与分析, 2021, 21(11): 1308-1312. CAI Xiaojun, WANG Lei, JIANG Bai|hua, et al. Intervention of Huangqi Guizhi Wuwu Decoction in rats with blood stasis syndrome based on liquid chromatography-quadrupole-time of flight-mass spectrometry blood metabolomics [J]. Evaluation and Analysis of Drug-Use in Hospitals of China, 2021, 21(11): 1308-1312.
[10] 王淑香. p38MAPK在心力衰竭发病机制中的研究进展[J]. 医学综述, 2014, 20(19): 3486-3488. WANG Shuxiang. Research progress of the role of p38MAPK in the pathogenesis of heart failure [J]. Medical Recapitulate, 2014, 20(19): 3486-3488.
[11] González A, Schelbert EB, Díez J, et al. Myocardial interstitial fibrosis in heart failure: biological and translational perspectives [J]. J Am Coll Cardiol, 2018, 71(15): 1696-1706.
[12] Yamagata K. Polyphenols regulate endothelial functions and reduce the risk of cardiovascular disease [J]. Curr Pharm Des, 2019, 25(22): 2443-2458.
[13] Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid [J]. Pharmacogn Rev, 2016, 10(20): 84-89.
[14] Batiha GE, Beshbishy AM, Ikram M, et al. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: quercetin [J]. Foods, 2020, 9(3): E374.
[15] Mirsafaei L, Reiner Ž, Shafabakhsh R, et al. Molecular and biological functions of quercetin as a natural solution for cardiovascular disease prevention and treatment [J]. Plant Foods Hum Nutr, 2020, 75(3): 307-315.
[16] Sharma A, Parikh M, Shah H, et al. Modulation of Nrf2 by quercetin in doxorubicin-treated rats [J]. Heliyon, 2020, 6(4): e03803.
[17] Ma C, Xia R, Yang S, et al. Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE-/- mice [J]. Theranostics, 2020, 10(3): 1090-1106.
[18] Tay KC, Tan LT, Chan CK, et al. Formononetin: a review of its anticancer potentials and mechanisms [J]. Front Pharmacol, 2019, 10: 820. doi: 10.3389/fphar.2019.00820.
[19] Ma X, Wang J. Formononetin: a pathway to protect neurons [J]. Front Integr Neurosci, 2022, 16: 908378. doi: 10.3389/fnint.2022.908378.
[20] Wang DS, Yan LY, Yang DZ, et al. Formononetin ameliorates myocardial ischemia/reperfusion injury in rats by suppressing the ROS-TXNIP-NLRP3 pathway [J]. Biochem Biophys Res Commun, 2020, 525(3): 759-766.
[21] Aonuma K, Ferdousi F, Xu D, et al. Effects of isorhamnetin in human amniotic epithelial stem cells in vitro and its cardioprotective effects in vivo [J]. Front Cell Dev Biol, 2020, 8: 578197. doi: 10.3389/fcell.2020.578197.
[22] Gao L, Yao R, Liu Y, et al. Isorhamnetin protects against cardiac hypertrophy through blocking PI3K-AKT pathway [J]. Mol Cell Biochem, 2017, 429(1-2): 167-177.
[23] Du Y, Han J, Zhang H, et al. Kaempferol prevents against ang II-induced cardiac remodeling through attenuating ang II-induced inflammation and oxidative stress [J]. J Cardiovasc Pharmacol, 2019, 74(4): 326-335.
[24] Puzianowska-Kuznicka M. ESR1 in myocardial infarction [J]. Clin Chim Acta, 2012, 413(1-2): 81-87.
[25] Kolur V, Vastrad B, Vastrad C, et al. Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis [J]. BMC Cardiovasc Disord, 2021, 21(1): 329.
[26] Peter I, Huggins GS, Shearman AM, et al. Age-related changes in echocardiographic measurements: association with variation in the estrogen receptor-alpha gene [J]. Hypertension, 2007, 49(5): 1000-1006.
[27] Yokota T, Li J, Huang J, et al. p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart [J]. J Clin Invest, 2020, 130(10): 5287-5301.
[28] 段卡丹, 张守彦, 李松森, 等. MAPK信号通路在转化生长因子β1诱导心肌成纤维细胞趋化运动中的作用[J]. 中国动脉硬化杂志, 2020, 28(11): 966-971. DUAN Kadan, ZHANG Shouyan, LI Songsen, et al. Roles of MAPK signaling pathway on chemotaxis of cardiac fibroblasts induced by transforming growth factor-Β [J]. Chinese Journal of Arteriosclerosis, 2020, 28(11): 966-971.
[29] 刘婷婷, 张淑萍, 覃筱燕, 等. MAPK信号转导通路与神经损伤研究进展[J]. 中国公共卫生, 2016, 32(2): 248-254. LIU Tingting, ZHANG Shuping, QIN Xiaoyan, et al. Progress in studies on MAPK signal transduction pathway and nerve injury [J]. Chinese Journal of Public Health, 2016, 32(2): 248-254.
[30] Sinfield JK, Das A, ORegan DJ, et al. p38 MAPK alpha mediates cytokine-induced IL-6 and MMP-3 expression in human cardiac fibroblasts [J]. Biochem Biophys Res Commun, 2013, 430(1): 419-424.
[31] Romero-Becerra R, Santamans AM, Folgueira C, et al. p38 MAPK pathway in the heart: new insights in health and disease [J]. Int J Mol Sci, 2020, 21(19): E7412.
[32] Lei J, Xue S, Wu W, et al. Sdc1 overexpression inhibits the p38 MAPK pathway and lessens fibrotic ventricular remodeling in MI rats [J]. Inflammation, 2013, 36(3): 603-615.
[33] Gallo S, Vitacolonna A, Bonzano A, et al. ERK: a key player in the pathophysiology of cardiac hypertrophy [J]. Int J Mol Sci, 2019, 20(9): 2164.
[34] 杨水健, 张鑫, 杨大春. p38 MAPK及基质金属蛋白酶在心力衰竭病人心肌重构中的意义[J]. 中国病理生理杂志, 2007, 23(8): 1631-1632. YANG Shuijian, ZHANG Xin, YANG Dachun. Significance of p38 MAPK and matrix metalloproteinases in myocardial remodeling of patients with contgestive heart failure [J]. Chinese Journal of Pathophysiology, 2007, 23(8): 1631-1632.
[35] Craige SM, Chen K, Blanton RM, et al. JNK and cardiometabolic dysfunction [J]. Biosci Rep, 2019, 39(7): BSR20190267.
[36] Cai H, Liu Y, Men H, et al. Protective mechanism of humanin against oxidative stress in aging-related cardiovascular diseases [J]. Front Endocrinol(Lausanne), 2021, 12: 683151. doi:10.3389/fendo.2021.683151.
[37] 周学红, 张晶. 白细胞介素-6和白细胞介素-17与急性心肌梗死相关性的研究进展[J]. 实用临床医药杂志, 2020, 24(1): 128-132. ZHOU Xuehong, ZHANG Jing. Research progress on the correlation between interleukin-6, interleukin-17 and acute myocardial infarction [J]. Journal of Clinical Medicine in Practice, 2020, 24(1): 128-132.
[38] Rai A, Narisawa M, Li P, et al. Adaptive immune disorders in hypertension and heart failure: focusing on T-cell subset activation and clinical implications [J]. J Hypertens, 2020, 38(10): 1878-1889.
[39] Xue GL, Li DS, Wang ZY, et al. Interleukin-17 upregulation participates in the pathogenesis of heart failure in mice via NF-κB-dependent suppression of SERCA2a and Cav1.2 expression [J]. Acta Pharmacologica Sinica, 2021, 42(11): 1780-1789.
[40] Zhou SF, Yuan J, Liao MY, et al. IL-17A promotes ventricular remodeling after myocardial infarction [J]. J Mol Med(Berl), 2014, 92(10): 1105-1116.
[41] Chang SL, Hsiao YW, Tsai YN, et al. Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK pathway in ischemic heart failure [J]. J Mol Cell Cardiol, 2018, 122: 69-79. doi:10.1016/j.yjmcc.2018.08.005.
[42] Hsiao YW, Tsai YN, Huang YT, et al. Rhodiola crenulata reduces ventricular arrhythmia through mitigating the activation of IL-17 and inhibiting the MAPK signaling pathway [J]. Cardiovasc Drugs Ther, 2021, 35(5): 889-900.
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