■本研究旨在研究北五味子水提物(SSAE)对酒精性肝病(ALD)的关键化学成分和作用及其相关分子机制。
■本研究采用UPLC-Q-TOF-MS/MS来鉴定SSAE中的化学成分。通过口服白酒建立ALD大鼠模型。转录组测序,加权基因共表达网络构建分析(WGCNA),和网络药理学用于预测SSAE治疗ALD的关键成分和途径。酶联免疫吸附测定(ELISA),生化试剂盒,苏木精-伊红(HE)染色,蛋白质印迹(WB)分析,和免疫组织化学分析用于验证SSAE治疗ALD的作用机制。
■活性成分,如五味子甲,五味子A,发现五味子醇B调节PI3K/AKT/IKK信号通路。与模型组相比,SSAE组显示ALD模型大鼠肝组织细胞凝固和组织炎症的显著改善。此外,SSAE调节谷草转氨酶(AST)的水平,丙氨酸氨基转移酶(ALT),乙醇脱氢酶(ADH),血清中的醛脱氢酶(ALDH)(P<0.05);免疫印迹和免疫组织化学分析显示,AKT,IKK,NFκB,和FOXO1蛋白在肝组织中显著降低(P<0.05),而Bcl-2蛋白表达水平显著升高(P<0.05)。
■SSAE的活性成分是五味子A,五味子A,和五味子B,调节PI3K的磷酸化水平,AKT,IKK,和NFκB和FOXO1蛋白的表达,并上调ALD大鼠肝组织Bcl-2蛋白的表达。这些发现表明SSAE部分通过PI3K-AKT-IKK信号传导途径对抗ALD。本研究为今后ALD的研究和治疗以及新型天然保肝药物的开发提供了参考。
UNASSIGNED: This study aimed to investigated the key chemical components and the effect of the aqueous extract of Schisandra sphenanthera (SSAE) on alcoholic liver disease (ALD) and the related molecular mechanism.
UNASSIGNED: This study employed UPLC-Q-TOF-MS/MS to identify the chemical compositions in SSAE. ALD rat model was established through oral administration of white spirit. Transcriptome sequencing, weighted gene co-expression network construction analysis (WGCNA), and network pharmacology were used to predict key compositions and pathways targeted by SSAE for the treatment of ALD. Enzyme-linked immunosorbent assay (ELISA), biochemical kits, hematoxylin-eosin (HE) staining, Western blotting (WB) analysis, and immunohistochemical analysis were used to validate the mechanism of action of SSAE in treating ALD.
UNASSIGNED: Active ingredients such as schisandrin A, schisandrol A, and schisandrol B were found to regulate the PI3K/AKT/IKK signaling pathway. Compared to the model group, the SSAE group demonstrated significant improvements in cellular solidification and tissue inflammation in the liver tissues of ALD model rats. Additionally, SSAE regulated the levels of a spartate aminotransferase (AST), alanine aminotransferase (ALT), alcohol dehydrogenase (ADH), and aldehyde Dehydrogenase (ALDH) in serum (P < 0.05); Western blotting and immunohistochemical analyses showed that the expression levels of phosphorylated PI3K, AKT, IKK, NFκB, and FOXO1 proteins were significantly reduced in liver tissues (P < 0.05), whereas the expression level of Bcl-2 proteins was significantly increased (P < 0.05).
UNASSIGNED: The active components of SSAE were schisandrin A, schisandrol A, and schisandrol B, which regulated the phosphorylation levels of PI3K, AKT, IKK, and NFκB and the expression of FOXO1 protein and upregulated the expression of Bcl-2 protein in the liver tissues of ALD rats. These findings indicate that SSAE acts against ALD partly through the PI3K-AKT-IKK signaling pathway. This study provided a reference for future research and treatment of ALD and the development of novel natural hepatoprotective drugs.