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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1448308
This article is part of the Research Topic Herbal Medicines and Their Metabolites: Effects on Lipid Metabolic Disorders via Modulating Oxidative Stress - Volume II View all 3 articles

Naringenin Modulates Oxidative Stress and Lipid Metabolism: Insights from Network Pharmacology, Mendelian Randomization, and Molecular Docking

Provisionally accepted
Jian Gao Jian Gao 1Linjie Yuan Linjie Yuan 2Huanyu Jiang Huanyu Jiang 3Li Ganggang Li Ganggang 3Yuwei Zhang Yuwei Zhang 3Ruijun Zhou Ruijun Zhou 3Wenjia Xian Wenjia Xian 3Yutong Zou Yutong Zou 3Quanyu Du Quanyu Du 1,4*Xianhua Zhou Xianhua Zhou 2
  • 1 Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
  • 2 Meishan Hospital, Chengdu University of Traditional Chinese Medicine, Meishan, China
  • 3 Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
  • 4 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, China

The final, formatted version of the article will be published soon.

    Previous studies have demonstrated that naringenin possesses lipid-lowering effects; however, the underlying mechanisms, particularly its specific molecular targets, remain uncertain. Using bioinformatics, three traditional Chinese medicine databases and one human disease database were integrated to establish two naringenin-target-hyperlipidemia modules: naringenin-oxidative stress (OS) and naringenin-lipid metabolism (LM). Data on 1,850 proteins from 1,871 genetic instruments were sourced from seven previous studies. Using Mendelian randomization based on data from the Integrative Epidemiology Unit genome-wide association study (case, n = 5,153; control, n = 344,069), we identified potential drug targets that were subsequently validated in the UK Biobank (396,565 individuals) and FinnGen (412,181 individuals) cohorts. Additionally, protein-protein interactions and protein-disease networks were analyzed to uncover potential connections between proteins and hyperlipidemia. In plasma, every standard deviation increase in apolipoprotein B (APOB) was associated with an increased risk of hyperlipidemia (odds ratio [OR] = 9.37, 95% confidence interval [CI], 5.12-17.12; P = 3.58e-13; posterior probability of hypothesis 4 [PPH4] = 0.997), and the same was observed for proprotein convertase subtilisin/kexin type 9 (OR = 1.81, 95% CI, 1.51-2.16; P = 6.87e-11; PPH4 = 1) and neurocan (OR = 2.34, 95% CI, 1.82-3.01; P = 4.09e-11; PPH4 = 0.932). The intersection of two modules and Mendelian randomization result identified APOB as a key regulatory target of naringenin in the treatment of hyperlipidemia. The binding energy between naringenin and APOB was determined to be -7.7 Kcal/mol. This Mendelian randomization-based analysis offers a robust framework for elucidating the pharmacological effects of naringenin and identifying candidate proteins for further investigation in the context of hyperlipidemia treatment.

    Keywords: Naringenin, Oxidative Stress, Lipid Metabolism, Mendelian randomization, Hyperlipidemia, Proprotein convertase subtilisin/kexin type 9, Apolipoprotein B, Neurocan

    Received: 13 Jun 2024; Accepted: 27 Sep 2024.

    Copyright: © 2024 Gao, Yuan, Jiang, Ganggang, Zhang, Zhou, Xian, Zou, Du and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Quanyu Du, Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.