Xu Yingyin, Xie Liyuan, Tang Jie, He Xiaolan, Zhang Zhiyuan, Chen Ying, Zhou Jie, Gan Bingcheng, Peng Weihong
National-Local Joint Engineering Laboratory of Edible and Medicinal Fungi, Agricultural Resources and Environment Institute, Sichuan Academy of Agricultural Science, Chengdu, China.
Scientific Observing and Experimental Station of Agro-microbial Resource and Utilization in Southwest China, Ministry of Agriculture, Chengdu, China.
Front Physiol. 2021 Aug 3;12:669331. doi: 10.3389/fphys.2021.669331. eCollection 2021.
This study aimed to investigate the effects of polysaccharides (MIPs) on carbon tetrachloride (CCl)-induced hepatic damage in mice. A total of 144 female mice were randomly assigned to four treatment groups, namely, control, CCl, low-dose MIP (LMIP) group, and high-dose MIP (HMIP) group. After the 10-day experiment, serum and liver were sampled for biochemical and metabolomic analyses. The HMIPs markedly decreased the liver weight under CCl intoxication. Furthermore, the significantly elevated concentrations of five serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, and total bile acid under CCl treatment were subverted by MIP administration in a dose-dependent manner. Moreover, MIPs relieved the increased hepatic malonaldehyde and protein carbonyl content and the decreased superoxide dismutase and catalase contents caused by CCl intoxication. There was also a dose-dependent decrease in the CCl-induced inflammatory indices, such as the levels of interleukin-1, interleukin-6, tumor necrosis factor-alpha, and myeloperoxidase, with MIP administration. Subsequent ultra-high performance liquid chromatography-tandem mass spectrometry-based serum metabolomics identified nine metabolites between the control and CCl groups and 10 metabolites between the HMIP and CCl groups, including some critical metabolites involved in flavonoid biosynthesis, amino acid metabolism, energy metabolism, and toxicant degradation. These novel findings indicate that MIPs may be of therapeutic value in alleviating the oxidative stress and inflammation caused by CCl. Liquid chromatography-mass spectrometry-based metabolomics provides a valuable opportunity for identifying potential biomarkers and elucidating the protective mechanisms of medicinal mushrooms against hepatic oxidative injury.
本研究旨在探讨多糖（MIPs）对四氯化碳（CCl）诱导的小鼠肝损伤的影响。总共144只雌性小鼠被随机分为四个治疗组，即对照组、CCl组、低剂量MIP（LMIP）组和高剂量MIP（HMIP）组。经过10天的实验后，采集血清和肝脏样本进行生化和代谢组学分析。HMIPs在CCl中毒情况下显著降低了肝脏重量。此外，CCl处理后显著升高的五个血清生化参数，包括丙氨酸转氨酶、天冬氨酸转氨酶、甘油三酯、总胆固醇和总胆汁酸的浓度，通过MIP给药以剂量依赖性方式得到了扭转。此外，MIPs缓解了CCl中毒引起的肝脏丙二醛和蛋白质羰基含量增加以及超氧化物歧化酶和过氧化氢酶含量降低的情况。随着MIP给药，CCl诱导的炎症指标，如白细胞介素-1、白细胞介素-6、肿瘤坏死因子-α和髓过氧化物酶水平，也呈现出剂量依赖性下降。随后基于超高效液相色谱-串联质谱的血清代谢组学鉴定出对照组和CCl组之间有9种代谢物，HMIP组和CCl组之间有10种代谢物，包括一些参与黄酮类生物合成、氨基酸代谢、能量代谢和毒物降解的关键代谢物。这些新发现表明，MIPs在减轻CCl引起的氧化应激和炎症方面可能具有治疗价值。基于液相色谱-质谱的代谢组学为识别潜在生物标志物和阐明药用蘑菇对肝脏氧化损伤的保护机制提供了宝贵机会。
