Amelioration of Alcoholic Liver Disease by Activating PXR-Cytochrome P450s Axis with Blackberry Extract
Ting Xiao,
Zhenghong Guo,
Min Fu,
Jiaoyan Huang,
Xiaowei Wang,
Yuqing Zhao,
Ling Tao,
Xiangchun Shen
Affiliations
Ting Xiao
The State Key Laboratory of Functions and Applications of Medicinal Plants, The Department of Pharmaceutic Preparation of Chinse Medicine, The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China
Zhenghong Guo
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
Min Fu
The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
Jiaoyan Huang
The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
Xiaowei Wang
The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China
Yuqing Zhao
School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China
Ling Tao
The State Key Laboratory of Functions and Applications of Medicinal Plants, The Department of Pharmaceutic Preparation of Chinse Medicine, The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China
Xiangchun Shen
The State Key Laboratory of Functions and Applications of Medicinal Plants, The Department of Pharmaceutic Preparation of Chinse Medicine, The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China
Blackberry is widely used in diets for its rich biological phytochemicals and health benefits. However, the relationship between the effect of blackberry extract (BBE) on ameliorating alcoholic liver disease (ALD) and the PXR-Cytochrome P450s axis in vivo and in vitro is unknown. In this study, 50% and 30% ethanol by gavage were used to establish acute and subacute ALD. Male mice were intragastrically administered BBE with 25, 50, and 100 mg/kg BW in the treatment groups. In the experiment, samples were collected, and related indices and histopathological observation were measured. In addition, the potential mechanism was predicted by network and docking studies, which were verified by qRT-PCR analysis, the detection of apoptosis, the measurement of mitochondrial membrane potential, the detection of ROS levels, and Western blotting in liver tissues and HepG2 cells. The acute and subacute ALD experiments indicated BBE ameliorated liver indices, AST, ALT, SOD, and MDA in serum, and the histopathology changed, as observed via H&E, Sirius red, and oil red O staining. The potential mechanism was predicted by network and docking studies, which were verified by experiments. Western blotting suggested BBE reduced the protein expression of NF-κB, TGF-β, IL-6, and α-SMA, and enhanced PXR and CAR in livers. In addition, qRT-PCR showed BBE significantly elevated the mRNA levels of PXR, CAR, CYP3A25, CYP3A11, and CYP2B10. In the experiment of the ethanol-induced apoptosis of HepG2 cells, BBE reduced the apoptosis of HepG2 cells by boosting mitochondrial membrane potential, reducing the apoptotic rate and ROS content, lessening the expression of Bax, and inducing the expression of PXR. For the first time, this study demonstrated BBE’s preventive effects on ALD, which are associated with the antioxidation and stimulation of the PXR-Cytochrome P450s axis. In addition, BBE is available as a nutritional agent.
