Top

Published in:

20-02-2024 | Active Ingredients | Research

Uncovering the Mechanism of Chinese Hawthorn Leaf on Myocardial Ischemia Based on Network Pharmacology, Molecular Docking Verification, and In Vitro Studies

Authors: Jingyun Gao, Yueyue Wang, Hui Xiong, Shengnan Zhao, Mingmei He, Meiting He, Haifeng Pan

Published in: Cardiovascular Toxicology | Issue 2/2024

Abstract

Hawthorn leaf has shown therapeutic effects in the patients with myocardial ischemia. Our study combines network pharmacology, molecular docking techniques, and in vitro experiment with the aim of revealing the mechanism of hawthorn leaves in the treatment of myocardial ischemia. The active ingredients and corresponding targets of hawthorn leaf through Traditional Chinese Medicine System Pharmacology and Swiss Target Prediction databases. Targets related to myocardial ischemia were retrieved by Gene Card, Online Mendelian Inheritance in Man, Disgenet, and Therapeutic Targets Database databases. Cytoscape software was used to construct an ingredient–target–organ network and enrichment analysis of common targets was analyzed. Molecular docking verification of the core compound and target interactions was performed using MOE software. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. Six active components and 107 potential therapeutic targets were screened. The protein–protein interaction network analysis indicated that 10 targets, including AKT1 and EGFR, were hub genes. Quercetin, kaempferol and isorhamnetin were taken as core active components. Through pathway enrichment analysis, nearly 455 Gene Ontology entries and 77 Kyoto Encyclopedia of Genes and Genomes pathways were obtained, mainly including PI3K/Akt, estrogen and other signaling pathways. Molecular docking prediction showed that three main active ingredients were firmly combined with the core targets. Cellular experiments showed that quercetin alleviated oxidative damage in cells and regulated the expression of PI3K, P-AKT/AKT and Bax/Bcl-2 proteins. This study identified the potential targets of Hawthorn leaf against myocardial ischemia using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Hawthorn leaf in treatment of myocardial ischemia.

Available only for authorised users

National Pharmacopoeia Commission. (2015). Pharmacopoeia of the people’s republic of China. China Medical Science and Technology Press.

Wu, J., Peng, W., Qin, R., & Zhou, H. (2014). Crataegus pinnatifida: Chemical constituents, pharmacology and potential applications. Molecules (Basel, Switzerland), 19(2), 1685–1712. https://doi.org/10.3390/molecules19021685CrossRefPubMed

Wen, K., Fang, X., Yang, J., Yao, Y., Nandakumar, K. S., Salem, M. L., & Cheng, K. (2021). Recent research on flavonoids and their biomedical applications. Current Medicinal Chemistry, 28(5), 1042–1066. https://doi.org/10.2174/0929867327666200713184138CrossRefPubMed

Chen, Z., & Zhang, S. L. (2021). The role of flavonoids in the prevention and management of cardiovascular complications: a narrative review. Annals of Palliative Medicine, 10(7), 8254–8263. https://doi.org/10.21037/apm-21-1343CrossRefPubMed

Zang, Z. Z., Chen, L. M., Liu, Y., Guan, Y. M., Du, Q., Xu, P., Shen, Q., Yang, M., Liu, H. N., & Liao, Z. G. (2021). Uncovering the protective mechanism of the volatile oil of Acorus tatarinowii against acute myocardial ischemia injury using network pharmacology and experimental validation. Evidence-Based Complementary and Alternative Medicine: ECAM, 2021, 6630795. https://doi.org/10.1155/2021/6630795CrossRefPubMed

Finegold, J. A., Asaria, P., & Francis, D. P. (2013). Mortality from ischaemic heart disease by country, region, and age: Statistics from World Health Organisation and United Nations. International Journal of Cardiology, 168(2), 934–945. https://doi.org/10.1016/j.ijcard.2012.10.046CrossRefPubMed

Xie, F., Wu, Y. Y., Duan, G. J., Wang, B., Gao, F., Wei, P. F., Chen, L., Liu, A. P., & Li, M. (2021). Anti-myocardial ischemia reperfusion injury mechanism of dried ginger-aconite decoction based on network pharmacology. Frontiers in Pharmacology, 12, 609702. https://doi.org/10.3389/fphar.2021.609702CrossRefPubMedPubMedCentral

Practise Guideline. (2020). For integrated management of cardiovascular diseases in primary hospitals. Chinese Medical Journal, 12(08), 1–73.

Li, M. Y. (2019). Progress of Chinese and Western medicine research on asymptomatic myocardial ischemia in coronary heart disease. Journal of Yellow River Institute of Science and Technology, 02, 7–12. https://doi.org/10.19576/j.issn.1008-5424.2019.02.003CrossRef

10.

Currò, D., Ianiro, G., Pecere, S., Bibbò, S., & Cammarota, G. (2017). Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders. British Journal of Pharmacology, 174(11), 1426–1449. https://doi.org/10.1111/bph.13632CrossRefPubMed

11.

Luo, L., Wang, H., Huang, G., Zhang, L., Li, X., Ma, C., & Wang, X. (2022). Pharmacological mechanisms of Tinglizi against chronic heart failure determined by network pharmacology and molecular docking. Evidence-Based Complementary and Alternative Medicine: ECAM, 2022, 2152399. https://doi.org/10.1155/2022/2152399CrossRefPubMed

12.

Hu, Y. W. (2021). Target prediction and clinical data validation of Fufang Banmao capsule for treating hepatocellular carcinoma based on network pharmacology. Nanchang University. https://doi.org/10.27232/d.cnki.gnchu.2021.000018CrossRef

13.

Wu, L., Chen, Y., Chen, M., Yang, Y., Che, Z., Li, Q., You, X., & Fu, W. (2021). Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus-Scorpion against prostate cancer. Andrologia, 53(9), e14165. https://doi.org/10.1111/and.14165CrossRefPubMed

14.

Tang, M. (2021). In vitro pharmacodynamic test study of antimyocardial ischemia of Tianxiangdan based on network pharmacology. Xinjiang Medical University.

15.

Li, Y., & Jeon, J. (2013). Quercetin modulates PTEN-Akt pathway to inhibit H2O2-induced apoptosis in vascular endothelial cells. Chinese Journal of Atherosclerosis, 12, 1089–1092.

16.

An, H. Y. (2016). Huang L j academic thoughts and clinical experience, and restenosis after interventional treatment of the coronary heart disease clinical research. Beijing University of Chinese Medicine.

17.

Hu, S. S. (2021). The writing committee of the report on cardiovascular health and diseases in China. China Cardiovascular Journal, 26(03), 209–218.

18.

Yue, D. F., & Li, Y. F. (2022). Research progress on the mechanism of action of Chinese medicine and its compound against myocardial ischemia-reperfusion injury. Chinese Pharmacology and Clinical, 06, 224–239. https://doi.org/10.13412/j.cnki.zyyl.20220313.003CrossRef

19.

Zhao, H., Yuan, L., Chen, Z., Liao, Y., & Lin, J. (2021). Exploring the diagnostic effectiveness for myocardial ischaemia based on CCTA myocardial texture features. BMC Cardiovascular Disorders, 21(1), 416. https://doi.org/10.1186/s12872-021-02206-zCrossRefPubMedPubMedCentral

20.

Editorial board of Chinese Journal of Cardiovascular Diseases. (2019). Expert consensus on early antithrombotic therapy and inter-hospital transport in patients with acute coronary syndrome. Clinical Medical Research and Practice (Chin), 4(18), 201.

21.

Ferenczyova, K., Kalocayova, B., Kindernay, L., Jelemensky, M., Balis, P., Berenyiova, A., Zemancikova, A., Farkasova, V., Sykora, M., Tothova, L., Jasenovec, T., Radosinska, J., Torok, J., Cacanyiova, S., Barancik, M., & Bartekova, M. (2020). Quercetin exerts age-dependent beneficial effects on blood pressure and vascular function, but is inefficient in preventing myocardial ischemia-reperfusion injury in Zucker diabetic fatty rats. Molecules (Basel, Switzerland), 25(1), 187. https://doi.org/10.3390/molecules25010187CrossRefPubMed

22.

Chen, L., Sun, L., Liu, Z., Wang, H., & Xu, C. (2016). Protection afforded by quercetin against H₂O₂-induced apoptosis on PC12 cells via activating PI3K/Akt signal pathway. Journal of Receptor and Signal Transduction Research, 36(1), 98–102. https://doi.org/10.3109/10799893.2015.1049363CrossRefPubMed

23.

Li, S. S., Li, P., Kang, N., Yuan, J., & Li, J. L. (2021). Research progress on the relationship between PI3K/AKT signaling pathway and cardiovascular disease. Beijing Medicine, 43(01), 66–69.

24.

Chu, D., & Zhang, Z. (2018). Trichosanthis pericarpium aqueous extract protects H9c2 cardiomyocytes from hypoxia/reoxygenation injury by regulating PI3K/Akt/NO pathway. Molecules (Basel, Switzerland), 23(10), 2409. https://doi.org/10.3390/molecules23102409CrossRefPubMed

Title: Uncovering the Mechanism of Chinese Hawthorn Leaf on Myocardial Ischemia Based on Network Pharmacology, Molecular Docking Verification, and In Vitro Studies
Authors: Jingyun Gao
Yueyue Wang
Hui Xiong
Shengnan Zhao
Mingmei He
Meiting He
Haifeng Pan
Publication date: 20-02-2024
Publisher: Springer US
Keyword: Active Ingredients
Published in: Cardiovascular Toxicology / Issue 2/2024
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-024-09825-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Uncovering the Mechanism of Chinese Hawthorn Leaf on Myocardial Ischemia Based on Network Pharmacology, Molecular Docking Verification, and In Vitro Studies

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2024

Hsa_circ_0032389 Enhances Proliferation and Migration in PDGF-BB-Induced Human Aortic Vascular Smooth Muscle Cells

Blockade of ZFX Alleviates Hypoxia-Induced Pulmonary Vascular Remodeling by Regulating the YAP Signaling

Cardioprotective Effects of Leucine Supplementation against Doxorubicin-Induced Cardiotoxicit

Effects of Electronic Cigarette Vaping on Cardiac and Vascular Function, and Post-myocardial Infarction Remodeling in Rats

Management of Fluoropyrimidine-Induced Cardiac Adverse Outcomes Following Cancer Treatment

The Role of mTOR in Doxorubicin-Altered Cardiac Metabolism: A Promising Therapeutic Target of Natural Compounds