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代谢组学分析揭示了槲皮素-3-O-半乳糖苷(金丝桃苷)对乙酰氨基酚诱导的小鼠肝损伤的保护作用。

Metabolomics analysis reveals the protective effect of quercetin-3-O-galactoside (Hyperoside) on liver injury in mice induced by acetaminophen.

作者信息

Hu Cheng, Chen Ying, Cao Yiyuan, Jia Yiqun, Zhang Jiaqi

机构信息

Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

J Food Biochem. 2020 Oct;44(10):e13420. doi: 10.1111/jfbc.13420. Epub 2020 Aug 3.

DOI:10.1111/jfbc.13420
PMID:32744346
Abstract

We investigated the protective effect of Hyperoside (HPS) on liver injury induced by acetaminophen (APAP) in C57 mice. HPS was administered orally for 7 days and APAP was administered orally on the 7th day. Serum and liver samples were then collected for biochemical analyses, histopathology assessments, and metabolomics studies. Metabolites were assessed using a UHPLC-MS system. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to process the data. Pathway analyses were performed using Metaboanalyst 4.0. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. HPS interacted with active sites in CYP2E1 and caused protein degradation. In conclusion, our results suggested that HPS prevented the oxidative stress-induced liver injury caused by APAP. PRACTICAL APPLICATIONS: Hyperoside was shown to have potential protective and therapeutic effects against liver diseases. Male C57 mice were used to perform pharmacodynamic, pharmacology, and metabolomics evaluations. At a dose of 60 mg/kg, HPS prevented oxidative stress-induced liver injury caused by APAP by regulating the glutathione-related metabolites and enzymes through the inhibition of CYP2E1.

摘要

我们研究了金丝桃苷(HPS)对乙酰氨基酚(APAP)诱导的C57小鼠肝损伤的保护作用。连续7天口服给予HPS,并在第7天口服给予APAP。随后收集血清和肝脏样本进行生化分析、组织病理学评估和代谢组学研究。使用超高效液相色谱-质谱联用系统(UHPLC-MS)评估代谢物。采用主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS-DA)处理数据。使用Metaboanalyst 4.0进行通路分析。分别采用蛋白质印迹法和qRT-PCR法测定蛋白质和mRNA水平。HPS与CYP2E1中的活性位点相互作用并导致蛋白质降解。总之,我们的结果表明,HPS可预防APAP引起的氧化应激诱导的肝损伤。实际应用:金丝桃苷对肝脏疾病具有潜在的保护和治疗作用。使用雄性C57小鼠进行药效学、药理学和代谢组学评估。在60mg/kg的剂量下,HPS通过抑制CYP2E1调节谷胱甘肽相关代谢物和酶,预防了APAP引起的氧化应激诱导的肝损伤。

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