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

doi:10.1016/j.heliyon.2024.e34214

The protective effects of aqueous extract of Schisandra sphenanthera against alcoholic liver disease partly through the PI3K-AKT-IKK signaling pathway

Heliyon. 2024 Jul 6;10(13):e34214. doi: 10.1016/j.heliyon.2024.e34214. eCollection 2024 Jul 15.

Authors

Ding Liu¹, Kai Yang¹, Taotao Li¹, Tiantian Tang¹, Yujiao Wang¹, Wenfei Wang¹, Jia Li¹, Peijie Zhou¹, Xuan Wang¹, Chongbo Zhao¹, Dongyan Guo¹, Yundong Xie¹, Jiangxue Cheng¹, Mei Wang¹, Jing Sun¹, Xiaofei Zhang^{1

2}

Affiliations

¹ Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanx, 712046, China.
² Key Laboratory of Modern Chinese Medicine Preparation, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, China.

Abstract

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.

Keywords: Alcoholic liver disease; Pharmacology; Schisandra sphenanthera; Transcriptome sequencing; UPLC-Q-TOF-MS/MS.