Full Text:   <800>

Summary:  <319>

Suppl. Mater.: 

CLC number: 

On-line Access: 2023-02-05

Received: 2022-04-11

Revision Accepted: 2022-09-25

Crosschecked: 2023-02-09

Cited: 0

Clicked: 1195

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Jianjia HUANG

https://orcid.org/0000-0002-0685-3237

Rongsheng SU

https://orcid.org/0000-0003-4574-5076

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.2 P.157-171

http://doi.org/10.1631/jzus.B2200213


Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways


Author(s):  Jianjia HUANG, Yuman BAI, Wenting XIE, Rongmei WANG, Wenyue QIU, Shuilian ZHOU, Zhaoxin TANG, Jianzhao LIAO, Rongsheng SU

Affiliation(s):  College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; more

Corresponding email(s):   srsh168@163.com

Key Words:  Acute liver injury, Oxidative stress, Mitochondrial dysfunction, Metabolomics, Lycium barbarum polysaccharides


Jianjia HUANG, Yuman BAI, Wenting XIE, Rongmei WANG, Wenyue QIU, Shuilian ZHOU, Zhaoxin TANG, Jianzhao LIAO, Rongsheng SU. Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways[J]. Journal of Zhejiang University Science B, 2023, 24(2): 157-171.

@article{title="Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways",
author="Jianjia HUANG, Yuman BAI, Wenting XIE, Rongmei WANG, Wenyue QIU, Shuilian ZHOU, Zhaoxin TANG, Jianzhao LIAO, Rongsheng SU",
journal="Journal of Zhejiang University Science B",
volume="24",
number="2",
pages="157-171",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200213"
}

%0 Journal Article
%T Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways
%A Jianjia HUANG
%A Yuman BAI
%A Wenting XIE
%A Rongmei WANG
%A Wenyue QIU
%A Shuilian ZHOU
%A Zhaoxin TANG
%A Jianzhao LIAO
%A Rongsheng SU
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 2
%P 157-171
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200213

TY - JOUR
T1 - Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways
A1 - Jianjia HUANG
A1 - Yuman BAI
A1 - Wenting XIE
A1 - Rongmei WANG
A1 - Wenyue QIU
A1 - Shuilian ZHOU
A1 - Zhaoxin TANG
A1 - Jianzhao LIAO
A1 - Rongsheng SU
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 2
SP - 157
EP - 171
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200213


Abstract: 
The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lycium barbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl4). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl4 solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl4-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase II detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I‒V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.

枸杞多糖通过降低氧化应激、保护线粒体功能和调节代谢途径改善犬急性肝损伤

黄健佳1,2,白雨曼1,谢文婷1,王荣梅3,邱文粤1,周水莲1,唐兆新1,廖建昭1,苏荣胜1
1华南农业大学兽医学院,中国广州,510642
2广州医药研究总院有限公司,中国广州,510240
3韶关大学生物与农业学院,中国韶关,512005
概要:急性肝损伤的发展可导致肝硬化、肝衰竭,甚至肝癌,但目前尚无有效的治疗方法。本研究旨在探讨枸杞多糖(LBPs)对四氯化碳(CCl4)诱导的急性肝损伤的保护作用及其治疗机制。为了建立急性肝损伤模型,以1 mL/kg的剂量对实验犬进行CCl4溶液的腹腔注射。然后给治疗组的实验犬喂食枸杞多糖(20 mg/kg)。微观结果显示,CCl4诱导的肝脏结构损伤、过度纤维化和线粒体密度降低都可以通过给予LBPs得到改善。LBPs可以通过抑制Kelch样ECH相关蛋白1(Keap1),促进蛋白(p62)、核因子E2相关因子2(Nrf2)和Nrf2下游的II期解毒基因和蛋白的产生,以及恢复过氧化氢酶(CAT)等抗氧化酶的活性,恢复并增加肝脏的抗氧化能力。LBPs还可以增强线粒体呼吸能力,提高组织ATP水平,以及重新激活呼吸链复合体I-V以减轻线粒体的损伤。血清代谢组学结果显示,LBPs对急性肝损伤的治疗作用主要通过控制脂质代谢途径实现。9-羟基十八碳二烯酸(9-HODE)、溶血磷脂酰胆碱(LPC)和磷脂酰乙醇胺(PE)可能是急性肝损伤的潜在标志物。这项研究证实,LBPs是一种有效的保肝药物,可以通过降低氧化应激、修复线粒体损伤和调节代谢途径来治疗急性肝损伤。

关键词:急性肝损伤;氧化应激;线粒体功能障碍;代谢组学;枸杞多糖

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]BalogunKA, AlbertCJ, FordDA, et al., 2013. Dietary omega-3 polyunsaturated fatty acids alter the fatty acid composition of hepatic and plasma bioactive lipids in C57BL/6 mice: a lipidomic approach. PLoS ONE, 8(11):e82399.

[2]BellezzaI, GiambancoI, MinelliA, et al., 2018. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res, 1865(5):721-733.

[3]BrandMD, NichollsDG, 2011. Assessing mitochondrial dysfunction in cells. Biochem J, 435(2):297-312.

[4]CaldezMJ, van HulN, KohHWL, et al., 2018. Metabolic remodeling during liver regeneration. Dev Cell, 47(4):‍425-438.e5.

[5]CalzadaE, AveryE, SamPN, et al., 2019. Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function. Nat Commun, 10:1432.

[6]ChenCF, WangK, ZhangHF, et al., 2019. A unique SUMO-interacting motif of Trx2 is critical for its mitochondrial presequence processing and anti-oxidant activity. Front Physiol, 10:1089.

[7]ChenYP, LiuKH, ZhangJW, et al., 2020. c-Jun NH2-terminal protein kinase phosphorylates the Nrf2-ECH homology 6 domain of nuclear factor erythroid 2-related factor 2 and downregulates cytoprotective genes in acetaminophen-induced liver injury in mice. Hepatology, 71(5):1787-1801.

[8]DuX, ZhangJJ, LiuL, et al., 2022. A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(4):286-299.

[9]ElvasF, StroobantsS, WyffelsL, 2017. Phosphatidylethanolamine targeting for cell death imaging in early treatment response evaluation and disease diagnosis. Apoptosis, 22(8):971-987.

[10]FrazierAE, VincentAE, TurnbullDM, et al., 2020. Assessment of mitochondrial respiratory chain enzymes in cells and tissues. Methods Cell Biol, 155:121-156.

[11]GaoJ, FengZH, WangXQ, et al., 2018. SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress. Cell Death Differ, 25(2):‍229-240.

[12]GonzalezE, van LiempdS, Conde-VancellsJ, et al., 2012. Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver injury reveals potential biomarkers for hepatotoxicity. Metabolomics, 8(6):997-1011.

[13]GouZX, SuXJ, HuX, et al., 2020. Melatonin improves hypoxic-ischemic brain damage through the Akt/Nrf2/Gpx4 signaling pathway. Brain Res Bull, 163:40-48.

[14]GuoQ, ZhangQQ, ChenJQ, et al., 2017. Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl4-induced liver injury. Chin J Nat Med, 15(7):525-533.

[15]HagaS, Yimin, OzakiM, 2017. Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis. BMC Gastroenterol, 17:9.

[16]Hinkovska-GalchevaV, TreadwellT, ShillingfordJM, et al., 2021. Inhibition of lysosomal phospholipase A2 predicts drug-induced phospholipidosis. J Lipid Res, 62:100089.

[17]HuW, DangXB, WangG, et al., 2018. Peroxiredoxin-3 attenuates traumatic neuronal injury through preservation of mitochondrial function. Neurochem Int, 114:120-126.

[18]JainA, LamarkT, SjøttemE, et al., 2010. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem, 285(29):22576-22591.

[19]JiaR, LiY, CaoLP, et al., 2019. Antioxidative, anti-inflammatory and hepatoprotective effects of resveratrol on oxidative stress-induced liver damage in tilapia (Oreochromis niloticus). Comp Biochem Physiol C Toxicol Pharmacol, 215:56-66.

[20]JardimFR, de AlmeidaFJS, LuckachakiMD, et al., 2020. Effects of sulforaphane on brain mitochondria: mechanistic view and future directions. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(4):263-279.

[21]JinY, HuangZL, LiL, et al., 2019. Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway. Acta Pharmacol Sin, 40:75-85.

[22]JohnsonCH, IvanisevicJ, SiuzdakG, 2016. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol, 17(7):451-459.

[23]KandelJ, AngelinAA, WallaceDC, et al., 2016. Mitochondrial respiration is sensitive to cytoarchitectural breakdown. Integr Biol (Camb), 8(11):1170-1182.

[24]LarsenS, NielsenJ, HansenCN, et al., 2012. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol, 590(14):3349-3360.

[25]LewisKN, WasonE, EdreyYH, et al., 2015. Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc Natl Acad Sci USA, 112(12):3722-3727.

[26]LinSY, XuD, DuXX, et al., 2019. Protective effects of salidroside against carbon tetrachloride (CCl4)‍-induced liver injury by initiating mitochondria to resist oxidative stress in mice. Int J Mol Sci, 20(13):3187.

[27]LiuBX, ZengQW, ChenHM, et al., 2021. The hepatotoxicity of altrazine exposure in mice involves the intestinal microbiota. Chemosphere, 272:129572.

[28]LiuJZ, WangX, LiuR, et al., 2014. Oleanolic acid co-administration alleviates ethanol-induced hepatic injury via Nrf-2 and ethanol-metabolizing modulating in rats. Chem Biol Interact, 221:88-98.

[29]LiuWW, ZhouY, DuanWZ, et al., 2021. Glutathione peroxidase 4-dependent glutathione high-consumption drives acquired platinum chemoresistance in lung cancer-derived brain metastasis. Clin Transl Med, 11(9):e517.

[30]LustgartenMS, BhattacharyaA, MullerFL, et al., 2012. Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels. Biochem Biophys Res Commun, 422(3):515-521.

[31]MaJ, YuJ, SuXR, et al., 2014. UPLC-MS-based serum metabonomics for identifying acute liver injury biomarkers in Chinese miniature pigs. Toxicol Lett, 225(3):358-366.

[32]MaQ, 2010. Transcriptional responses to oxidative stress: pathological and toxicological implications. Pharmacol Ther, 125(3):376-393.

[33]MaciejewskaD, DrozdA, Skonieczna-ŻydeckaK, et al., 2020. Eicosanoids in nonalcoholic fatty liver disease (NAFLD) progression. Do serum eicosanoids profile correspond with liver eicosanoids content during NAFLD development and progression? Molecules, 25(9):2026.

[34]MyersCR, 2012. The effects of chromium (VI) on the thioredoxin system: implications for redox regulation. Free Radic Biol Med, 52(10):2091-2107.

[35]OsthuesT, ZimmerB, RimolaV, et al., 2020. The lipid receptor G2A (GPR132) mediates macrophage migration in nerve injury-induced neuropathic pain. Cells, 9(7):1740.

[36]QiaoN, YangYY, LiaoJZ, et al., 2021. Metabolomics and transcriptomics indicated the molecular targets of copper to the pig kidney. Ecotoxicol Environ Saf, 218:112284.

[37]RaghunathA, SundarrajK, NagarajanR, et al., 2018. Antioxidant response elements: discovery, classes, regulation and potential applications. Redox Biol, 17:297-314.

[38]RalphSJ, Moreno-SánchezR, NeuzilJ, et al., 2011. Inhibitors of succinate: quinone reductase/Complex II regulate production of mitochondrial reactive oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death. Pharm Res, 28(11):2695-2730.

[39]RolinJ, Al-JaderiZ, MaghazachiAA, 2013. Oxidized lipids and lysophosphatidylcholine induce the chemotaxis and intracellular calcium influx in natural killer cells. Immunobiology, 218(6):875-883.

[40]SaitoK, MaekawaK, IshikawaM, et al., 2014. Glucosylceramide and lysophosphatidylcholines as potential blood biomarkers for drug-induced hepatic phospholipidosis. Toxicol Sci, 141(2):377-386.

[41]SharmaS, BhattaraiS, AraH, et al., 2020. SOD2 deficiency in cardiomyocytes defines defective mitochondrial bioenergetics as a cause of lethal dilated cardiomyopathy. Redox Biol, 37:101740.

[42]SheltonP, JaiswalAK, 2013. The transcription factor NF-E2-related factor 2 (Nrf2): a protooncogene? FASEB J, 27(2):414-423.

[43]SunHY, HuYJ, ZhaoXY, et al., 2015. Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP‍–Trx2‍–‍ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex. FEBS J, 282(14):2758-2774.

[44]TianXJ, LiangTS, LiuYL, et al., 2019. Extraction, structural characterization, and biological functions of Lycium barbarum polysaccharides: a review. Biomolecules, 9(9):389.

[45]TuWJ, WangH, LiS, et al., 2019. The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging Dis, 10(3):‍637-651.

[46]VanceJE, 2015. Phospholipid synthesis and transport in mammalian cells. Traffic, 16(1):1-18.

[47]VenâncioC, AntunesL, FélixL, et al., 2013. Chronic ketamine administration impairs mitochondrial complex I in the rat liver. Life Sci, 93(12-14):464-470.

[48]WangM, WangL, HanL, et al., 2017. The effect of carabrone on mitochondrial respiratory chain complexes in Gaeumannomyces graminis. J Appl Microbiol, 123(5):‍1100-1110.

[49]WuZG, HanMF, ChenT, et al., 2010. Acute liver failure: mechanisms of immune-mediated liver injury. Liver Int, 30(6):782-794.

[50]XinYF, ZhangS, GuLQ, et al., 2011. Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs. Biol Pharm Bull, 34(10):1523-1526.

[51]XuDW, XuM, JeongS, et al., 2019. The role of Nrf2 in liver disease: novel molecular mechanisms and therapeutic approaches. Front Pharmacol, 9:1428.

[52]ZhangJQ, ShiL, XuXN, et al., 2014. Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 15(12):1039-1047.

[53]ZhangQ, ZhangW, LiuJ, et al., 2021. Lysophosphatidylcholine promotes intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells via an orphan G protein receptor 2-mediated signaling pathway. Bioengineered, 12(1):4520-4535.

[54]ZhaoYN, LuJ, MaoAK, et al., 2021. Autophagy inhibition plays a protective role in ferroptosis induced by alcohol via the p62‍–‍Keap1–Nrf2 pathway. J Agric Food Chem, 69(33):9671-9683.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE