The protective effects of aqueous extract of Schisandra sphenanthera against alcoholic liver disease partly through the PI3K-AKT-IKK signaling pathway
Ding Liu,
Kai Yang,
Taotao Li,
Tiantian Tang,
Yujiao Wang,
Wenfei Wang,
Jia Li,
Peijie Zhou,
Xuan Wang,
Chongbo Zhao,
Dongyan Guo,
Yundong Xie,
Jiangxue Cheng,
Mei Wang,
Jing Sun,
Xiaofei Zhang
Affiliations
Ding Liu
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Kai Yang
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Taotao Li
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Tiantian Tang
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Yujiao Wang
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Wenfei Wang
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Jia Li
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Peijie Zhou
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Xuan Wang
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Chongbo Zhao
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Dongyan Guo
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Yundong Xie
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Jiangxue Cheng
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Mei Wang
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China
Jing Sun
Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China; Corresponding author. School of Pharmacy Shaanxi University of Chinese Medicine. Xianyang, China.
Xiaofei Zhang
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; Corresponding author. School of Pharmacy Shaanxi University of Chinese Medicine. Xianyang, China.
Purpose: 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. Methods: 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. Results: 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). Conclusion: 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.
