Mechanism of Action of NvZhen ErXian HeJi in Ovariectomized Rats with Myocardial Infarction based on Network Pharmacology


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Objective:NvZhen ErXian HeJi (NZEXHJ) is used to treat perimenopausal syndrome (PS), but its effect on perimenopausal coronary heart disease is unclear. Furthermore, the aim of this research is to study the effect of NZEXHJ on perimenopausal coronary heart disease (PMCHD) in a rat model based on a network pharmacology approach.

Materials and Methods:Based on network pharmacological analysis combined with molecular docking, we predicted the potential therapeutic target and pharmacological mechanism of NZEXHJ in the treatment of PMCHD. We used an ovariectomized rat (OVR) model to understand the effect of NZEXHJ on myocardial injury and further verified the target of NZEXHJ in the intervention of PMCHD.

Results:We selected 52 active components of NZEXHJ against PMCHD and an intersection of their targets on network pharmacology, to which SCN5A, SER1, AR, and PGR were significantly correlated. The protein- protein interaction network revealed CASP3, CXCL8, IL6, MAPK1, TNF, TP53, and VEGFA in the treatment of PMCHD with NZEXHJ. Kaempferol, luteolin, and mistletoe presented good affinity towards the aforementioned targets by Molecular docking NZEXHJ exerted protecting cardiomyocytes for OVR. The mechanism was related to a reduction in the expression levels of the CXCL8, TNF, and regulating PI3K-AKT signaling pathways.

Conclusion:This study reveals the potential multi-component, multi-target, and multi-pathway pharmacological effects of NZEXHJ and predicts its protection against myocardial infarction in ovariectomized rats through the PI3K Akt pathway, providing a theoretical basis for the treatment of PMCHD.

Sobre autores

Kai Wu

Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Shuxun Guo

Department of Cardiology,, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Jie Zhang

Department of Cardiology,, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Desong Wen

Department of Cardiology,, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Linli Zhang

Department of Cardiology,, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Mingyang Zhu

Department of Cardiology,, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Xiulong Wang

Department of Cardiology,, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Xuefang Li

Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University

Email: info@benthamscience.net

Zhigang Chen

Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University

Autor responsável pela correspondência
Email: info@benthamscience.net

Fei Lin

Department of Cardiology,, The First Affiliated Hospital of Xinxiang Medical University

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Jesmin S, Sakuma I, Hattori Y, Kitabatake A. In vivo estrogen manipulations on coronary capillary network and angiogenic molecule expression in middle-aged female rats. Arterioscler Thromb Vasc Biol 2002; 22(10): 1591-7. doi: 10.1161/01.ATV.0000034929.42459.0D PMID: 12377735
  2. Honigberg MC, Zekavat SM, Niroula A, et al. Premature menopause, clonal hematopoiesis, and coronary artery disease in postmenopausal women. Circulation 2021; 143(5): 410-23. doi: 10.1161/CIRCULATIONAHA.120.051775 PMID: 33161765
  3. Genazzani AR, Monteleone P, Giannini A, Simoncini T. Hormone therapy in the postmenopausal years: Considering benefits and risks in clinical practice. Hum Reprod Update 2021; 27(6): 1115-50. doi: 10.1093/humupd/dmab026 PMID: 34432008
  4. Cho L, Kaunitz AM, Faubion SS, et al. Rethinking menopausal hormone therapy: For whom, what, when, and how long? Circulation 2023; 147(7): 597-610. doi: 10.1161/CIRCULATIONAHA.122.061559 PMID: 36780393
  5. Song YH, Li BS, Chen XM, Cai H. Ethanol extract from Epimedium brevicornum attenuates left ventricular dysfunction and cardiac remodeling through down-regulating matrix metalloproteinase-2 and -9 activity and myocardial apoptosis in rats with congestive heart failure. Int J Mol Med 2008; 21(1): 117-24. doi: 10.3892/ijmm.21.1.117 PMID: 18097624
  6. Li T-T, Guo Y-J, Ren J, Liu H, Ji ES. Danggui Buxue decoction improves heart function of chronic intermittent hypoxia mice by promoting mitochondrial autophagy and inhibiting cardiomyocyte apoptosis. Zhongguo Zhongyao Zazhi 2022; 47(11): 3066-72. PMID: 35718531
  7. Zhang Y, Diao T-Y, Wang L. Protective effects of water fraction of Fructus Ligustri Lucidi extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice. J Ethnopharmacol 2014; 158: Pt A239. doi: 10.1016/j.jep.2014.10.025
  8. Zhang Y, Liu L, Gao J, et al. New secoiridoids from the fruits of Ligustrum lucidum ait with triglyceride accumulation inhibitory effects. Fitoterapia 2013; 91: 107-12. doi: 10.1016/j.fitote.2013.08.022 PMID: 24001714
  9. Zhang DF, Zhu Z, Li LH, Jin X, Fang JW. Er-xian decoction, a traditional Chinese herbal formula, intervening early in hypothalamic-pituitary axis of male rats with delayed puberty. Pharmacogn Mag 2014; 10(40): 517-21. doi: 10.4103/0973-1296.141780 PMID: 25422555
  10. Wong KC, Lee KS, Luk HK, et al. Er-xian decoction exerts estrogen-like osteoprotective effects in vivo and in vitro. Am J Chin Med 2014; 42(2): 409-26. doi: 10.1142/S0192415X1450027X PMID: 24707871
  11. Jiashuo WU, Fangqing Z, Zhuangzhuang LI. Integration strategy of network pharmacology in traditional Chinese medicine: A narrative review. J Tradit Chin Med 2022; 42(3): 479-86.
  12. Gao E, Lei YH, Shang X, et al. A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse. Circ Res 2010; 107(12): 1445-53. doi: 10.1161/CIRCRESAHA.110.223925 PMID: 20966393
  13. Clarkson TB. Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause 2018; 25(11): 1262-74. doi: 10.1097/GME.0000000000001228 PMID: 30358722
  14. Zhang GQ, Chen JL, Luo Y, et al. Menopausal hormone therapy and women’s health: An umbrella review. PLoS Med 2021; 18(8): e1003731. doi: 10.1371/journal.pmed.1003731 PMID: 34339416
  15. Khan ZA, Janssen I, Mazzarelli JK, et al. Serial studies in subclinical atherosclerosis during menopausal transition (from the study of Women’s Health Across the Nation). Am J Cardiol 2018; 122(7): 1161-8. doi: 10.1016/j.amjcard.2018.06.039 PMID: 30077316
  16. Stevenson JC, Tsiligiannis S, Panay N. Cardiovascular risk in perimenopausal women. Curr Vasc Pharmacol 2019; 17(6): 591-4. doi: 10.2174/1570161116666181002145340 PMID: 30280667
  17. Lu J, Liu G, Wang Z, Cao J, Chen Y, Dong Y. Restraint stress induces uterine microenvironment disorder in mice during early pregnancy through the β2-AR/cAMP/PKA pathway. Stress 2021; 24(5): 514-28. doi: 10.1080/10253890.2020.1855419 PMID: 33280472
  18. Kim HI, Kim TH, Yoo JY, et al. ARID1A and PGR proteins interact in the endometrium and reveal a positive correlation in endometriosis. Biochem Biophys Res Commun 2021; 550: 151-7. doi: 10.1016/j.bbrc.2021.02.144 PMID: 33706098
  19. Holthoff HP, Zeibig S, Jahns-Boivin V, et al. Detection of anti-β1-AR autoantibodies in heart failure by a cell-based competition ELISA. Circ Res 2012; 111(6): 675-84. doi: 10.1161/CIRCRESAHA.112.272682 PMID: 22811559
  20. Zhang X, Yoon JY, Morley M, et al. A common variant alters SCN5A–miR-24 interaction and associates with heart failure mortality. J Clin Invest 2018; 128(3): 1154-63. doi: 10.1172/JCI95710 PMID: 29457789
  21. Chang H, Li C, Huo K, et al. Luteolin prevents H2O2-induced apoptosis in H9C2 cells through modulating Akt-P53/Mdm2 signaling pathway. BioMed Res Int 2016; 2016: 1-9. doi: 10.1155/2016/5125836 PMID: 27525270
  22. Li C, Wang T, Zhang C, Xuan J, Su C, Wang Y. Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways. Gene 2016; 577(2): 275-80. doi: 10.1016/j.gene.2015.12.012 PMID: 26680104
  23. Lin HM, Yen FL, Ng LT, Lin CC. Protective effects of Ligustrum lucidum fruit extract on acute butylated hydroxytoluene-induced oxidative stress in rats. J Ethnopharmacol 2007; 111(1): 129-36. doi: 10.1016/j.jep.2006.11.004 PMID: 17157464
  24. Gao HX, Liang HY, Chen N, Shi B, Zeng WC. Potential of phenolic compounds in Ligustrum robustum (Rxob.) Blume as antioxidant and lipase inhibitors: Multi-spectroscopic methods and molecular docking. J Food Sci 2022; 87(2): 651-63. doi: 10.1111/1750-3841.16020 PMID: 35122440
  25. Liu R, Hao D, Xu W, et al. β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice. Pharm Biol 2019; 57(1): 161-8. doi: 10.1080/13880209.2019.1577461 PMID: 30905278
  26. Qi Y, Ying Y, Zou J, et al. Kaempferol attenuated cisplatin-induced cardiac injury via inhibiting STING/NF-κB-mediated inflammation. Am J Transl Res 2020; 12(12): 8007-18. PMID: 33437376
  27. Zhang KK, Wang H, Qu D, et al. Luteolin alleviates methamphetamine-induced hepatotoxicity by suppressing the p53 pathway- mediated apoptosis, autophagy, and inflammation in rats. Front Pharmacol 2021; 12: 641917. doi: 10.3389/fphar.2021.641917 PMID: 33679421
  28. Farag MR, Moselhy AAA, El-Mleeh A. Quercetin alleviates the immunotoxic impact mediated by oxidative stress and inflammation induced by doxorubicin exposure in rats. Basel, Switzerland: Antioxidants 2021; p. 10.
  29. Yu L, Wei J, Liu P. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer. Semin Cancer Biol 2022; 85: 69-94. doi: 10.1016/j.semcancer.2021.06.019 PMID: 34175443
  30. Xu H, Li Y, Han B, et al. Anti-breast-cancer activity exerted by β-sitosterol-D-glucoside from sweet potato via upregulation of microRNA-10a and via the PI3K–Akt signaling pathway. J Agric Food Chem 2018; 66(37): 9704-18. doi: 10.1021/acs.jafc.8b03305 PMID: 30160115
  31. Zhang S, Cui R. The targeted regulation of miR-26a on PTEN-PI3K/Akt signaling pathway in myocardial fibrosis after myocardial infarction. Eur Rev Med Pharmacol Sci 2020; 24(18): 9235. PMID: 33015756
  32. Jin Z, Zhang W, Luo Y, et al. Protective effect of Qingre Huoxue decoction against myocardial infarction via PI3K/Akt autophagy pathway based on UPLC-MS, network pharmacology, and in vivo evidence. Pharm Biol 2021; 59(1): 1605-16. doi: 10.1080/13880209.2021.2001542 PMID: 34818128
  33. Yang X, Li X, Lin Q, Xu Q. Up-regulation of microRNA-203 inhibits myocardial fibrosis and oxidative stress in mice with diabetic cardiomyopathy through the inhibition of PI3K/Akt signaling pathway via PIK3CA. Gene 2019; 715: 143995. doi: 10.1016/j.gene.2019.143995 PMID: 31336140
  34. Liu C, Yang J, Fu W, et al. Coactivation of the PI3K/Akt and ERK signaling pathways in PCB153-induced NF-κB activation and caspase inhibition. Toxicol Appl Pharmacol 2014; 277(3): 270-8. doi: 10.1016/j.taap.2014.03.027 PMID: 24726520
  35. Meng H, Zhang Y, An ST, Chen Y. Annexin A3 gene silencing promotes myocardial cell repair through activation of the PI3K/Akt signaling pathway in rats with acute myocardial infarction. J Cell Physiol 2019; 234(7): 10535-46. doi: 10.1002/jcp.27717 PMID: 30456911
  36. Janas A, Kruczek E, Londzin P, Borymski S, Czuba ZP, Folwarczna J. Negligible effect of estrogen deficiency on development of skeletal changes induced by type 1 diabetes in experimental rat models. Mediators Inflamm 2020; 2020: 1-21. doi: 10.1155/2020/2793804 PMID: 33204216
  37. Wegorzewska IN, Walters K, Weiser MJ, et al. Postovariectomy weight gain in female rats is reversed by estrogen receptor α agonist, propylpyrazoletriol. Am J Obstet Gynecol 2008; 199(1): 67.e1-5. doi: 10.1016/j.ajog.2007.11.054 PMID: 18241818
  38. Vakili S, Zal F, Mostafavi-pour Z, Savardashtaki A, Koohpeyma F. Quercetin and vitamin E alleviate ovariectomy-induced osteoporosis by modulating autophagy and apoptosis in rat bone cells. J Cell Physiol 2021; 236(5): 3495-509. doi: 10.1002/jcp.30087 PMID: 33030247
  39. Calabrese EJ, Agathokleous E, Kapoor R, Dhawan G, Calabrese V. Luteolin and hormesis. Mech Ageing Dev 2021; 199: 111559. doi: 10.1016/j.mad.2021.111559 PMID: 34403687
  40. Sharma AR, Nam JS. Kaempferol stimulates Wnt/β-catenin signaling pathway to induce differentiation of osteoblasts. J Nutr Biochem 2019; 74: 108228. doi: 10.1016/j.jnutbio.2019.108228 PMID: 31678747
  41. Wang N, Wang L, Yang J, Wang Z, Cheng L. Quercetin promotes osteogenic differentiation and antioxidant responses of mouse bone mesenchymal stem cells through activation of the AMPK/ SIRT1 signaling pathway. Phytother Res 2021; 35(5): 2639-50. doi: 10.1002/ptr.7010 PMID: 33421256

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