Ganoderma lucidum Polysaccharides Ameliorate Acetaminophen-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Apoptosis along the Nrf2 Pathway

被引:7
作者
Zhang, Nan [1 ,2 ,3 ]
Han, Zhongming [2 ]
Zhang, Rui [2 ]
Liu, Linling [1 ,3 ]
Gao, Yanliang [1 ,3 ]
Li, Jintao [1 ,3 ]
Yan, Meixia [1 ,3 ]
机构
[1] Chinese Acad Agr Sci, Inst Special Anim & Plant Sci, Changchun 130112, Peoples R China
[2] Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
[3] Jilin Prov Key Lab Tradit Chinese Med Mat Cultivat, Changchun 130112, Peoples R China
关键词
Ganoderma lucidum polysaccharides; acute liver injury; oxidative stress; Nrf2 signaling pathway;
D O I
10.3390/nu16121859
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI). Ganoderma lucidum polysaccharides (GLPs) exhibit hepatoprotective activity, yet the protective impact and potential mechanism of GLPs in relation to APAP-induced ALI remain ambiguous. The intention of this research was to scrutinize the effect of GLPs on APAP-induced ALI and to shed light on their potential mechanism. The results demonstrated that GLPs were capable of notably alleviating the oxidative stress triggered by APAP, as shown through a significant drop in the liver index, the activities of serum ALT and AST, and the amounts of ROS and MDA in liver tissue, along with an increase in the levels of SOD, GSH, and GSH-Px. Within these, the hepatoprotective activity at the high dose was the most conspicuous, and its therapeutic efficacy surpassed that of the positive drug (bifendate). The results of histopathological staining (HE) and apoptosis staining (TUNEL) indicated that GLPs could remarkably inhibit the necrosis of hepatocytes, the permeation of inflammatory cells, and the occurrence of apoptosis induced by APAP. Moreover, Western blot analysis manifested that GLPs enhanced the manifestation of Nrf2 and its subsequent HO-1, GCLC, and NQO1 proteins within the Nrf2 pathway. The results of qPCR also indicated that GLPs augmented the expression of antioxidant genes Nrf2, HO-1, GCLC, and NQO1. The results reveal that GLPs are able to set off the Nrf2 signaling path and attenuate ALI-related oxidative stress and apoptosis, which is a potential natural medicine for the therapy of APAP-induced liver injury.
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页数:17
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共 40 条
[1]   Ganoderma lucidum: Persuasive biologically active constituents and their health endorsement [J].
Ahmad, Md Faruque .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 107 :507-519
[2]   Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for acetaminophen overdose [J].
Akakpo, Jephte Y. ;
Ramachandran, Anup ;
Curry, Steven C. ;
Rumack, Barry H. ;
Jaeschke, Hartmut .
ARCHIVES OF TOXICOLOGY, 2022, 96 (02) :453-465
[3]   TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence [J].
Bird, Thomas G. ;
Mueller, Miryam ;
Boulter, Luke ;
Vincent, David F. ;
Ridgway, Rachel A. ;
Lopez-Guadamillas, Elena ;
Lu, Wei-Yu ;
Jamieson, Thomas ;
Govaere, Olivier ;
Campbell, Andrew D. ;
Ferreira-Gonzalez, Sofia ;
Cole, Alicia M. ;
Hay, Trevor ;
Simpson, Kenneth J. ;
Clark, William ;
Hedley, Ann ;
Clarke, Mairi ;
Gentaz, Pauline ;
Nixon, Colin ;
Bryce, Steven ;
Kiourtis, Christos ;
Sprangers, Joep ;
Nibbs, Robert J. B. ;
Van Rooijen, Nico ;
Bartholin, Laurent ;
McGreal, Steven R. ;
Apte, Udayan ;
Barry, Simon T. ;
Iredale, John P. ;
Clarke, Alan R. ;
Serrano, Manuel ;
Roskams, Tania A. ;
Sansom, Owen J. ;
Forbes, Stuart J. .
SCIENCE TRANSLATIONAL MEDICINE, 2018, 10 (454)
[4]   Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management [J].
Bjornsson, Hk ;
Bjornsson, Es .
EUROPEAN JOURNAL OF INTERNAL MEDICINE, 2022, 97 :26-31
[5]   USP25 regulates KEAP1-NRF2 anti-oxidation axis and its inactivation protects acetaminophen-induced liver injury in male mice [J].
Cai, Changzhou ;
Ma, Huailu ;
Peng, Jin ;
Shen, Xiang ;
Zhen, Xinghua ;
Yu, Chaohui ;
Zhang, Pumin ;
Ji, Feng ;
Wang, Jiewei .
NATURE COMMUNICATIONS, 2023, 14 (01)
[6]   Astaxanthin Activated the Nrf2/HO-1 Pathway to Enhance Autophagy and Inhibit Ferroptosis, Ameliorating Acetaminophen-Induced Liver Injury [J].
Cai, Xiaopeng ;
Hua, Shiyuan ;
Deng, Jingwen ;
Du, Zhen ;
Zhang, Dongxiao ;
Liu, Zhenfeng ;
Khan, Nazif Ullah ;
Zhou, Min ;
Chen, Zhi .
ACS APPLIED MATERIALS & INTERFACES, 2022, 14 (38) :42887-42903
[7]   Role and mechanisms of autophagy in acetaminophen-induced liver injury [J].
Chao, Xiaojuan ;
Wang, Hua ;
Jaeschke, Hartmut ;
Ding, Wen-Xing .
LIVER INTERNATIONAL, 2018, 38 (08) :1363-1374
[8]   Hepatoprotective effect of Phellinus linteus mycelia polysaccharide (PL-N1) against acetaminophen-induced liver injury in mouse [J].
Chen, Chen ;
Liu, Xiang ;
Qi, Shanshan ;
Dias, Alberto C. P. ;
Yan, Jingkun ;
Zhang, Xiaoying .
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2020, 154 :1276-1284
[9]   Hepatocyte-specific Mas activation enhances lipophagy and fatty acid oxidation to protect against acetaminophen-induced hepatotoxicity in mice [J].
Chen, Shuai ;
Lu, Zhi ;
Jia, Haoyu ;
Yang, Bo ;
Liu, Chun ;
Yang, Yuxin ;
Zhang, Shuo ;
Wang, Zhijing ;
Yang, Liu ;
Li, Shanshan ;
Li, Jing ;
Yang, Changqing .
JOURNAL OF HEPATOLOGY, 2023, 78 (03) :543-557
[10]   Anti-Inflammatory and Hepatoprotective Effects of Ganoderma lucidum Polysaccharides against Carbon Tetrachloride-Induced Liver Injury in Kunming Mice [J].
Chen, Yu-Sheng ;
Chen, Quan-Zhan ;
Wang, Zhen-Jiong ;
Hua, Chun .
PHARMACOLOGY, 2019, 103 (3-4) :143-150