体内
葡萄糖醛酸化
代谢途径
药理学
没食子酸
代谢物
鞣花酸
化学
生物化学
新陈代谢
轨道轨道
生物
微粒体
抗氧化剂
体外
多酚
色谱法
质谱法
生物技术
作者
Shumeng Ren,Qingzhu Zhang,Man Jiang,Menglin Chen,Xia-jing Xu,Dongmei Wang,Yingni Pan,Xiaoqiu Liu
标识
DOI:10.1016/j.jep.2021.114870
摘要
Walnut kernel, a well-known TCM, is often used after being defatted in tradition. And defatted walnut powder extract (DWPE) has the actions of tonifying the liver and kidney, dissipating stagnation and removing blood stasis, which has the effect on non-alcoholic fatty liver disease (NAFLD). However, the effective components of DWPE in vivo were unclear and the multiple mechanisms of DWPE against NAFLD have not been explored.The studies were performed to screen the effective substances in vivo by identification of the metabolites of DWPE in rats and to seek the potential mechanisms of DWPE on NAFLD by construction of the network pharmacology based on metabolites and verification of the highly correlated pathway.To explore the effective substances in vivo, the metabolites of DWPE were identified in SD rats' bio-samples through UPLC-Q-Exactive Orbitrap MS. To analyze the mechanisms of DWPE on NAFLD, a Metabolite-Target-Disease network was established and the potential mechanisms were predicted. Then, highly correlated pathway was verified in animal and cells studies.A total of 52 metabolites of DWPE were identified in vivo, which were derived from gallic acid, ellagic acid (EA) and glansreginin A (Gla A). The possible metabolic pathways were phase Ⅰ (hydroxylation, hydrolyzation, etc) and phase Ⅱ metabolic reactions (methylation, sulfation and glucuronidation). Furthermore, in the network pharmacology, 54 core targets were enriched into pathways in cancer, nitrogen metabolism and other 9 pathways, which were essential pathways of DWPE against NAFLD. And the mechanism of nitrogen metabolism was verified in both of animal and cells studies. The results showed that DWPE could decline the concentration of ammonia and increase the expressions of carbonic anhydrase 2 (CA2) and carbamoylphosphate synthetase (CPS1) in nitrogen metabolism.Taken together, the study revealed the absorption components and their metabolic pathways and demonstrated the mechanism of nitrogen metabolism of DWPE on anti-NAFLD.
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