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.
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.
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Acknowledgments
This work was supported by the Science and Technology Project of Shaoguan Science and Technology Bureau (No. 200811104530939). In addition, we would like to thank Na QIAO and Hanming CHEN from the Veterinary Medicine of South China Agricultural University for their help in the experiment and professional advice in the process of writing this manuscript.
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Jianjia HUANG: data curation, investigation, visualization, conceptualization, and writing original draft. Yuman BAI: formal analysis, investigation, and methodology. Wenting XIE: review and data curation. Rongmei WANG: funding acquisition. Wenyue QIU: investigation and conceptualization. Shuilian ZHOU: formal analysis. Zhaoxin TANG: resources. Jianzhao LIAO: writing, reviewing, and editing. Rongsheng SU: project administration, data curation, resources, supervision, writing, reviewing, and editing. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Jianjia HUANG, Yuman BAI, Wenting XIE, Rongmei WANG, Wenyue QIU, Shuilian ZHOU, Zhaoxin TANG, Jianzhao LIAO, and Rongsheng SU declare that they have no conflict of interest.
All institutional and national guidelines for the care and use of laboratory animals were followed. All experimental procedures and animal care were carried out in accordance with pertinent guidelines and regulations approved by the Institutional Animal Care and Use Committee of South China Agricultural University (No. 2020A132).
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Table S1; Figs. S1–S7; Materials and methods
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Huang, J., Bai, Y., Xie, W. et al. Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways. J. Zhejiang Univ. Sci. B 24, 157–171 (2023). https://doi.org/10.1631/jzus.B2200213
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DOI: https://doi.org/10.1631/jzus.B2200213
Key words
- Acute liver injury
- Oxidative stress
- Mitochondrial dysfunction
- Metabolomics
- Lycium barbarum polysaccharides