Liu Ding, Yang Kai, Li Taotao, Tang Tiantian, Wang Yujiao, Wang Wenfei, Li Jia, Zhou Peijie, Wang Xuan, Zhao Chongbo, Guo Dongyan, Xie Yundong, Cheng Jiangxue, Wang Mei, Sun Jing, Zhang Xiaofei
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China.
Key Laboratory of Modern Chinese Medicine Preparation, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, China.
Heliyon. 2024 Jul 6;10(13):e34214. doi: 10.1016/j.heliyon.2024.e34214. eCollection 2024 Jul 15.
This study aimed to investigated the key chemical components and the effect of the aqueous extract of (SSAE) on alcoholic liver disease (ALD) and the related molecular mechanism.
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 in treating ALD.
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).
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.
本研究旨在探究五味子水提取物（SSAE）的关键化学成分及其对酒精性肝病（ALD）的影响和相关分子机制。
本研究采用超高效液相色谱-四极杆飞行时间串联质谱（UPLC-Q-TOF-MS/MS）鉴定SSAE中的化学成分。通过口服白酒建立ALD大鼠模型。利用转录组测序、加权基因共表达网络构建分析（WGCNA）和网络药理学预测SSAE治疗ALD的关键成分和靶向通路。采用酶联免疫吸附测定（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验证SSAE治疗ALD的作用机制。
发现五味子醇甲、五味子醇A和五味子醇B等活性成分可调节PI3K/AKT/IKK信号通路。与模型组相比，SSAE组在ALD模型大鼠肝组织的细胞凝固和组织炎症方面有显著改善。此外，SSAE调节血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）的水平（P<0.05）；蛋白质印迹和免疫组织化学分析表明，肝组织中磷酸化PI3K、AKT、IKK、NFκB和FOXO1蛋白的表达水平显著降低（P<0.05），而Bcl-2蛋白的表达水平显著升高（P<0.05）。
SSAE的活性成分是五味子醇甲、五味子醇A和五味子醇B，它们调节ALD大鼠肝组织中PI3K、AKT、IKK和NFκB的磷酸化水平以及FOXO1蛋白的表达，并上调Bcl-2蛋白的表达。这些发现表明SSAE部分通过PI3K-AKT-IKK信号通路对抗ALD。本研究为未来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。
