Detection of Emodin Derived Glutathione Adduct in Normal Rats Administered with Large Dosage of Polygoni Multiflori Radix
نویسندگان
چکیده
Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. PMR-associated hepatotoxicity has been drawing increasingly more attention in recent years in parallel with its wide utilization. Anthraquinones (AQs) are recognized as the main hepatotoxic components in PMR. However, the exact underlying mechanism of AQs poisoning is still not fully understood. Herein, we proposed a hypothesis that metabolic activation of AQs such as emodin was involved in PMR-induced liver injury, AQs followed to generate the electrophilic reactive metabolites and subsequently formed covalent adduct with cellular nucleophiles in the liver to exert hepatotoxicity. In the present study, the link of cytotoxicity of PMR in primary human hepatocytes and the depletion of glutathione (GSH) was investigated by MTT assay and UHPLC-QqQ-MS/MS analysis. The results showed that PMR depleted GSH and therefore induced cytotoxicity. Then, emodin-GSH adduct was identified in bile of liver injured rats after intragastric administration of PMR or emodin with the aid of UHPLC-QTOF-MS/MS method. Our findings not only provided confirmative evidence that the mechanism of hepatotoxicity induced by AQs in PMR involved key metabolic steps, but also revealed that emodin-GSH adduct had potential to be further developed as a sensitive and traceable biomarker for the assessment of PMR-induced liver injury.
منابع مشابه
Comparison of raw and processed Radix Polygoni Multiflori (Heshouwu) by high performance liquid chromatography and mass spectrometry
BACKGROUND Radix Polygoni Multiflori is the dried root tuber of Polygonum multiflorum Thunb. (Fam. Polygonaceae). According to Chinese medicine theory, raw (R-RPM) and processed (P-RPM) Radix Polygoni Multiflori possess different properties. The present study investigates the differences in chemistry between raw and processed Radix Polygoni Multiflori. METHODS Five pairs of R-RPM and P-RPM as...
متن کاملThe Protective Effect of Radix Polygoni Multiflori on Diabetic Encephalopathy via Regulating Myosin Light Chain Kinase Expression
Currently there has been no effective treatment of diabetic encephalopathy. Radix Polygoni Multiflori, a famous traditional Chinese medicine, is widely used in antiaging treatment, especially in prevention and treatment of Alzheimer's diseases. In this study we tried to explore the effect of Radix Polygoni Multiflori on cognitive function among diabetic rats with demonstrated cognitive impairme...
متن کاملEffects of Lipid Regulation Using Raw and Processed Radix Polygoni Multiflori in Rats Fed a High-Fat Diet
Raw and processed Radix Polygoni Multiflori have been used in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD), hyperlipidemia, and related diseases in Asian counties for centuries. The lipid regulation ability of raw and processed Poligoni Multiflori Radix were compared in high-fat diet fed rats in this research. Total cholesterol (TC) and low density lipoprotein-choles...
متن کاملMajor Anthraquinones Derived from Polygoni Multiflori Radix Alter Bile Acid Disposition in Sandwich Cultured Rat Hepatocytes
متن کامل
Hepatotoxicity in Rats Induced by Aqueous Extract of Polygoni Multiflori Radix, Root of Polygonum multiflorum Related to the Activity Inhibition of CYP1A2 or CYP2E1
The objective of this study is to investigate the relationship between the hepatotoxicity induced by Polygoni Multiflori Radix (PMR, root of Polygonum multiflorum Thunb., He Shou Wu) and the activity of CYP1A2 or CYP2E1 in the rat liver. Levels of rat serum transaminases ALT and AST were not altered but the activity of CYP1A2 or CYP2E1 in the rat liver was significantly inhibited after oral adm...
متن کامل