Characteristics and Regulatory Mechanisms of Cholestatic Liver Injury Caused by Chinese Herbal Medicines
10.13422/j.cnki.syfjx.20241512
- VernacularTitle:探讨中药致胆汁淤积型肝损伤的特点及调控机制
- Author:
Yun YANG
1
;
Guozhuang ZHANG
1
;
Ting LIU
1
;
Yifei YANG
1
Author Information
1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China
- Publication Type:Journal Article
- Keywords:
Chinese herbal medicine;
cholestasis;
molecular docking;
network toxicology;
regulatory mechanisms
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(23):64-71
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the characteristics and regulatory mechanisms of cholestatic liver injury （CLI） caused by traditional Chinese medicine based on data mining， network pharmacology， and molecular docking. MethodChina National Knowledge Infrastructure and PubMed were searched for the relevant literature on CLI caused by traditional Chinese medicine from inception to 2024， and the information was standardized， summarized， and analyzed by cluster analysis. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）， GeneCards， Online Mendelian Inheritance in Man （OMIM）， and DisGeNET were used to retrieve the active ingredients and targets of core medicines. The Venn diagram was established to map the common targets shared by the core medicines and CLI. Cytoscape 3.10.2 was used to construct the protein-protein interaction （PPI） network of the common targets. DAVID was used for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment of the core targets. Finally， molecular docking was performed by AutoDock Vina. ResultA total of 849 eligible articles were included in this study， from which 64 active ingredients of 39 herbal medicines that can cause cholestasis were counted and categorized according to the 2020 edition of the Pharmacopoeia of the People's Republic of China. The frequency of the medidicnes followed a descending order of heat-clearing medicines， exterior-releasing medicines， blood-activating and stasis-resolving medicines， purgative medicines， phlegm-resolving and cough- and dyspnea-relieving medicines， tonics， wind- and dampness-expelling medicines， interior-warming medicines， urination-promoting and dampness-draining medicines， Qi movement-regulating medicines， hemostatics， toxin-removing， worm-killing， and itch-relieving medicines， astringent medicines， dampness-eliminating medicines， and tranquiling medicines. The cluster analysis revealed that the reports of CLI caused by heat-clearing medicines accounted for the highest proportion of 39.69%. Among the heat-clearing medicines， Gardeniae Fructus （92 articles， accounting for 10.84%）， Scutellariae Radix （76 articles， 8.95%）， and Sophorae Flavescentis Radix （69 articles， 6.95%） were frequently reported. The core targets of cholestasis induced by Chinese herbal medicines reported to cause CLI mainly included tumor necrosis factor （TNF）， peroxisome proliferator activated receptor alpha （PPARA）， farnesoid X receptor （FXR）， glutamic-pyruvic transaminase 2 （GPT2）， superoxide dismutase 1 （SOD1）， interferon gamma （IFN-γ）， interleukin-6（IL-6）， CD36， Apolipoprotein A1（APOA1）， Angiotensin converting enzyme（ACE）， Cytochrome P450 3A4 enzyme（CYP3A4）， Protein kinase B1（Akt1）， APOB， albumin（ALB）， ATP binding cassette transporter A4（ABCB4）， SLC10A1， Estrogen Receptor alpha （ESR1）， signal transducer and activator of transcription1（STAT1）， β-actin（ACTB）， Endothelin 1（EDN1）， ABCG2， and peroxisome proliferator activated receptor gamma（PPARG）. The signaling pathways involved included bile secretion， ABC transporter， steroid biosynthesis， DNA adducts， drug metabolism， cytochrome P450， peroxisomes， primary bile acid biosynthesis， retinol metabolism， and Toll-like receptor. The molecular docking results showed that the active ingredients （e.g.， baicalin and berberine） of the heat-clearing medicines reported by high frequency to cause CLI had high binding affinity to the targets including ABCG2， IFN-γ， EDN1， IL-6 and SOD1， with the binding energy in the range of -13 kcal·mol-1 to -9 kcal·mol-1， and the regulatory pathways were highly correlated with transporters， microvascular function regulation， inflammation， and oxidative stress， which was consistent with the cluster analysis. ConclusionThe available reports about the Chinese herbal medicines causing CLI mainly focused on heat-clearing medicines， and the core targets included ABCG2， IFN-γ， EDN1， IL-6， and SOD1. The regulatory pathways were mainly related to transporters， microvascular function regulation， inflammation， and oxidative stress.
