Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway

Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechan...

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Main Authors: Xiaomei Zheng, Xinyan Wu, Qiqi Wen, Huaqiao Tang, Ling Zhao, Fei Shi, Yinglun Li, Zhongqiong Yin, Yuanfeng Zou, Xu Song, Lixia Li, Xinghong Zhao, Gang Ye
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/20/4349
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author Xiaomei Zheng
Xinyan Wu
Qiqi Wen
Huaqiao Tang
Ling Zhao
Fei Shi
Yinglun Li
Zhongqiong Yin
Yuanfeng Zou
Xu Song
Lixia Li
Xinghong Zhao
Gang Ye
author_facet Xiaomei Zheng
Xinyan Wu
Qiqi Wen
Huaqiao Tang
Ling Zhao
Fei Shi
Yinglun Li
Zhongqiong Yin
Yuanfeng Zou
Xu Song
Lixia Li
Xinghong Zhao
Gang Ye
author_sort Xiaomei Zheng
collection DOAJ
description Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug. The in vivo experiment showed that eriodictyol can effectively reduce liver function-related biochemical indicators such as ALT, AST, and AKP. Eriodictyol can also up-regulate the levels of SOD and GSH, and inhibit the release of IL-1β, IL-6, and TNF-α. Additionally, TUNEL staining, immunohistochemistry, and RT-PCR experiments showed that eriodictyol activated the PI3K/AKT pathway and decreased the expression of Bax, caspase3, and caspase8 while increasing the expression of Bcl-2 m-RNA. Finally, molecular docking experiments and molecular dynamics simulations confirmed the stable binding between eriodictyol and PI3K, AKT molecules. This study showed that eriodictyol can activate the PI3K/AKT signaling pathway to alleviate ALI-related oxidative stress and apoptosis.
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spelling doaj.art-56deeca393d1407c8bc79c815dbd7f6c2023-11-19T17:37:30ZengMDPI AGNutrients2072-66432023-10-011520434910.3390/nu15204349Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling PathwayXiaomei Zheng0Xinyan Wu1Qiqi Wen2Huaqiao Tang3Ling Zhao4Fei Shi5Yinglun Li6Zhongqiong Yin7Yuanfeng Zou8Xu Song9Lixia Li10Xinghong Zhao11Gang Ye12College of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu 611130, ChinaEriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug. The in vivo experiment showed that eriodictyol can effectively reduce liver function-related biochemical indicators such as ALT, AST, and AKP. Eriodictyol can also up-regulate the levels of SOD and GSH, and inhibit the release of IL-1β, IL-6, and TNF-α. Additionally, TUNEL staining, immunohistochemistry, and RT-PCR experiments showed that eriodictyol activated the PI3K/AKT pathway and decreased the expression of Bax, caspase3, and caspase8 while increasing the expression of Bcl-2 m-RNA. Finally, molecular docking experiments and molecular dynamics simulations confirmed the stable binding between eriodictyol and PI3K, AKT molecules. This study showed that eriodictyol can activate the PI3K/AKT signaling pathway to alleviate ALI-related oxidative stress and apoptosis.https://www.mdpi.com/2072-6643/15/20/4349eriodictyolacute liver injurynetwork pharmacologyapoptosisPI3K/AKT signaling pathway
spellingShingle Xiaomei Zheng
Xinyan Wu
Qiqi Wen
Huaqiao Tang
Ling Zhao
Fei Shi
Yinglun Li
Zhongqiong Yin
Yuanfeng Zou
Xu Song
Lixia Li
Xinghong Zhao
Gang Ye
Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway
Nutrients
eriodictyol
acute liver injury
network pharmacology
apoptosis
PI3K/AKT signaling pathway
title Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway
title_full Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway
title_fullStr Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway
title_full_unstemmed Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway
title_short Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway
title_sort eriodictyol alleviated lps d galn induced acute liver injury by inhibiting oxidative stress and cell apoptosis via pi3k akt signaling pathway
topic eriodictyol
acute liver injury
network pharmacology
apoptosis
PI3K/AKT signaling pathway
url https://www.mdpi.com/2072-6643/15/20/4349
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