Mechanism of Action of Hawthorn Leaves against Hyperlipidemia Based on Network Pharmacology and Preliminary Validation Study

LIU Xuegui; LI Zhiming; LIU Changfeng; ZHOU Jingyao; WANG Yaoyao; GAO Pinyi; LI Danqi

doi:10.13386/j.issn1002-0306.2021100176

Volume 43 Issue 12

Jun. 2022

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Science and Technology of Food Industry > 2022 > 43(12): 36-45. > DOI: 10.13386/j.issn1002-0306.2021100176

LIU Xuegui, LI Zhiming, LIU Changfeng, et al. Mechanism of Action of Hawthorn Leaves against Hyperlipidemia Based on Network Pharmacology and Preliminary Validation Study[J]. Science and Technology of Food Industry, 2022, 43(12): 36−45. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021100176.

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Mechanism of Action of Hawthorn Leaves against Hyperlipidemia Based on Network Pharmacology and Preliminary Validation Study

LIU Xuegui^{1, 2,},
LI Zhiming³,
LIU Changfeng⁴,
ZHOU Jingyao³,
WANG Yaoyao³,
GAO Pinyi^3, ,,
LI Danqi^{1, 5, ,}

1.
Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang 110142, China
2.
National-Local Joint Engineering Laboratory for Development of Boron and Magnesium Resources and Fine Chemical Technology, Shenyang University of Chemical Technology, Shenyang 110142, China
3.
College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China
4.
College of Environment and Safety Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China
5.
Liaoning Province Key Laboratory of Green Functional Molecular Design and Development, Shenyang University of Chemical Technology, Shenyang 110142, China

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Received Date: October 17, 2021
Available Online: April 13, 2022

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Abstract

Abstract

Objective: Network pharmacology was used to predict potential compounds, targets and pathways of action in hawthorn leaves for the treatment of hyperlipidaemia, and the network pharmacology predictions were validated in conjunction with target enzyme and cellular assays. The material basis and mechanism of action of hawthorn leaves against hyperlipidemia. Methods: The chemical components of hawthorn leaves were obtained through the traditional Chinese Medicine System Pharmacology database analysis platform and literature mining, and the potential targets were obtained by using the relevant databases. GO and KEGG analysis were carried out to construct the “component-target-pathway” network. The effective components and potential targets predicted by network pharmacology were verified by ERK2 kinase, oil red O staining and triglyceride experiment. Results: After the network pharmacology screening, 96 active ingredients and 40 interacting target proteins were obtained from hawthorn leaves. The results of KEGG analysis indicated that the therapeutic effects of the active ingredient on hyperlipidaemia were mainly through the following signalling pathways: Metabolic pathway, AMPK signaling pathway, HIF-1 signaling pathway, insulin resistance, thyroid hormone signaling pathway. According to the prediction results of network pharmacology, combined with the representative compounds of hawthorn leaves isolated by the research group, the ERK2 kinase activity of six compounds such as vitexin was tested. The results showed that the inhibition rate of vitexin on ERK2 kinase was the highest, reaching 84%. By constructing high-fat HepG2 cell model, oil red O staining and quantitative experiment were carried out, and TG content was measured. It was found that after vitexin intervention, the number of lipid droplets in cells gradually decreased with the increasing of vitexin concentration, and TG content decreased, indicating that vitexin could reduce lipid accumulation and TG content in cells. Further, the results of network pharmacology predicted the anti hyperlipidemia effect of vitexin in hawthorn leaves were verified. Conclusion: In this paper, network pharmacology was used to predict the material basis and mechanism of action of compounds in hawthorn leaves against hyperlipidemia. Target enzyme, oil red O staining and TG quantification experiments initially confirmed the network pharmacology predictions, while suggesting that vitexin would be promising as a potential therapeutic compound for reducing intracellular lipid content.
- network pharmacology,
- hawthorn leaves,
- hyperlipidaemia,
- molecular docking,
- oil red O staining

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