Metabolomic study on the hepatotoxic or hepatoprotective effects of rhubarb to normal or hepatic fibrosis rats
10.16438/j.0513-4870.2018-0049
- VernacularTitle:基于代谢组学的大黄对正常和肝纤维化大鼠双向作用对比研究
- Author:
Can TU
1
;
Qin HE
2
;
Yuan-yuan ZHOU
1
;
Xiao-hui WANG
2
;
Le ZHANG
1
;
Lu-ge WEI
2
;
Ming NIU
2
;
Yu PANG
3
;
Xiao-he XIAO
2
;
Jia-bo WANG
2
Author Information
1. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
3. National Center for Adverse Drug Reaction Monitoring, Beijing 100020, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
rhubarb;
metabonomics;
hepatotoxicity;
hepatoprotective;
You Gu Wu Yun
- From:
Acta Pharmaceutica Sinica
2018;53(7):1139-1147
- CountryChina
- Language:Chinese
-
Abstract:
Focusing on the TCM-related adverse drug reactions, especially those conventionally non-toxic TCM induced hepatotoxicity, this paper has proposed and established the disease-syndrome-based toxicology evaluation pattern and approach for TCM, not only the normal rats, but the hepatic fibrosis model rat were studied hepatotoxic or hepatoprotective effects of rhubarb, meanwhile liver histopathology changes by histological tests such as HE and TUNEL staining. The metabolomics analysis method will be employed to screen the key metabolites and possible metabolic pathway of the dual effects of rhubarb in rats. The results showed that rhubarb could result in significant liver injury in normal rats, indicated by the elevation of plasma serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (P < 0.01), as well as liver histopathology changes by histological tests such as HE and TUNEL staining; whereas the levels of ALT and AST were significantly decreased in the model group of rhubarb, and the histopathology of liver was significantly improved. The UPLC-QTOF/MS methods were used to characterize the differences metabolites in contrast group plasma of rats. Eventually, seven potential biomarkers such as taurine, L-arginine, creatine, L-valine, retinyl ester, and prostaglandin F2α were confirmed by multivariate statistical analysis and metabolic pathways enrichment analysis linked to six metabolic pathways, including taurine and hypotaurine metabolism, primary bile acid biosynthesis, arginine and proline metabolism, arachidonic acid metabolism, retinol metabolism and valine, leucine and isoleucine biosynthesis. In summary, the results suggested the dual effects of rhubarb screened by taurine and hypotaurine metabolism, primary bile acid biosynthesis and arginine and proline metabolism may be the key metabolic pathway related to You Gu Wu Yun phenomenon of rhubarb. This study will provide new vision and illustration of scientific evidences for the hepatotoxicity assessment and rational use of those drugs containing anthraquinones.
