Exploration on the Molecular Mechanism of Dioscoreae Bulbiferae Rhizoma in Inducing Hepatotoxicity through Cholestasis Based on Transcriptomics
10.19879/j.cnki.1005-5304.202405206
- VernacularTitle:基于转录组学探讨黄药子诱导胆汁淤积致肝脏毒性的分子机制
- Author:
Wanxi HOU
1
;
Caidong WU
;
Qibo LEI
;
Kaihong ZANG
Author Information
1. 甘肃中医药大学药学院,甘肃 兰州 730000
- Publication Type:Journal Article
- Keywords:
Dioscoreae Bulbiferae Rhizoma;
hepatotoxicity;
transcriptomics;
cholestasis
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(4):85-91
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the hepatotoxicity of Dioscoreae Bulbiferae Rhizoma and its molecular mechanism using transcriptomics.Methods Totally 40 SPF-grade male Kunming mice were randomly divided into the normal control group and Dioscoreae Bulbiferae Rhizoma low-,medium-and high-dosage groups,and were orally administered with the decoction of Dioscoreae Bulbiferae Rhizoma for 14 days.Serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)contents were detected,HE staining was used for morphology examination of the liver and scoring,transcriptomic analysis was conducted to detect the gene expression of liver tissue,differentially expressed genes were subjected to GO and KEGG pathway enrichment analysis,serum alkaline phosphatase(ALP)and total bile acid(TBA)content in liver tissue were detected,Western blot was used to validate key targets.Results Compared with the normal control group,Dioscoreae Bulbiferae Rhizoma high-dosage group showed an increase in serum ALT and AST contents(P<0.05),with hepatic cell edema,increased volume,dilated hepatic sinusoids,necrosis in some areas,and elevated pathological score(P<0.05).Transcriptomic analysis revealed that after intervention with Dioscoreae Bulbiferae Rhizoma,differentially expressed genes in liver tissue were mainly enriched in cholesterol metabolism process,steroid metabolism process,cholesterol biosynthesis process,and signaling pathways such as steroid biosynthesis,cholesterol metabolism,bile secretion and primary bile acid biosynthesis.The experimental verification results showed that serum ALP and liver tissue TBA content in Dioscoreae Bulbiferae Rhizoma high-dosage group increased(P<0.05),as well as HMGCS1 and CYP51A1,the expressions of CYP27A1 and CYP7A1,which promoted cholesterol conversion to bile acids in liver tissue increased(P<0.05,P<0.01),while the expression of multidrug resistance protein 4(MRP4),which promoted bile acid excretion decreased(P<0.05).Conclusion Dioscoreae Bulbiferae Rhizoma inducing liver toxicity is related to promoting cholesterol synthesis and conversion into bile acids,while inhibiting bile acid excretion.
