Mechanisms of Fufang Biejia Ruangan Pills Against Alcoholic Liver Disease via Regulating Liver-brain Dialogue Mediated by HMGB1-BDNF Axis
10.13422/j.cnki.syfjx.20241638
- VernacularTitle:从HMGB1-BDNF互作轴所介导的肝-脑对话探讨复方鳖甲软肝片干预酒精性肝病的作用机制
- Author:
Yudong LIU
1
;
Xiangying YAN
1
;
Tao LI
1
;
Chu ZHANG
2
;
Bingbing CAI
2
;
Zhaochen MA
1
;
Na LIN
1
;
Yanqiong ZHANG
1
Author Information
1. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs， Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China
2. College of Pharmacy， Fujian University of Traditional Chinese Medicine， Fuzhou 350122， China
- Publication Type:Journal Article
- Keywords:
alcoholic liver disease;
liver-brain axis;
Fufang Biejia Ruangan pills;
γ-aminobutyric acid
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(23):214-223
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills （FBRP） in the intervention of alcoholic liver disease （ALD） using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group， model group， and FBRP low-， medium-， and high-dose groups （9.6， 19.2， 38.4 mg·kg-1）. Except for the normal group， the remaining groups were given 56° white wine by gavage to establish the acute ALD model， with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group， model group， and FBRP medium-dose group （19.2 mg·kg-1）. The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin （HE）， Sirius Red， oil red O staining， and enzyme-linked immunosorbent assay （ELISA）. Intoxication behaviors of each group were objectively evaluated through sobering-up time， net-catching， and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue， with experimental validation by ELISA， Western blot， and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in liver tissues of mice in the acute and chronic ALD model groups were significantly increased （P<0.05）. Compared with the model group， the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased （P<0.05）. Compared with the normal group， the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks （P<0.01）. Compared with the model group， the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks （P<0.05）. Compared with the normal group， the expression of high mobility group protein B1 （HMGB1） protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased （P<0.01）. Compared with the model group， the expression of HMGB1 protein in FBRP medium dose group was significantly decreased （P<0.05，P<0.01）. Compared with the normal group， the expression of brain-derived neurotrophic factor （BDNF） protein and the release of γ-aminobutyric acid （GABA） in the prefrontal cortex of the model group were significantly decreased （P<0.01）. Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased （P<0.05）. ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.
