Interpretation the Hepatotoxicity Based on Pharmacokinetics Investigated Through Oral Administrated Different Extraction Parts of Polygonum multiflorum on Rats

Frontiers in Pharmacology

Lei Yan¹  Longfei Lin²  Hongmei Lin³  Changhai Qu³  Miao Zhang³  Jian Ni³ 

[1] Fengtai District Community Health Center, Beijing, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China;School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China;

关键词: Polygonum multiflorum;    hepatotoxicity;    pharmacokinetics;    LC-MS/MS;    different extraction parts;   

DOI  :  10.3389/fphar.2018.00505

来源: DOAJ

【 摘 要 】

The liver injury induced by Polygonum multiflorum (PM) used for clinical treatment has recently received widespread attention. This study aimed to determine the hepatotoxicity of PM through pharmacokinetics studies. The extract of PM was separated to isolate the anthraquinone fraction, the tannin and polysaccharide fraction, the hydroxystilbene fraction, and the combined anthraquinone fraction. A rapid LC-MS/MS method was developed and validated to simultaneously analyze 2,3,5,4′-tetrahydroxystilbene-2-O-β-glucoside (TSG), emodin-8-O-β-D-glucopyranoside (EDG), and emodin in rat plasma, and was applied to the pharmacokinetics (PK) studies. The hepatotoxicity of different extracted parts of PM was evaluated through the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) in rat serum. The results showed that liver injury occurred in all the treated groups and that the hepatotoxicity performance of the total extract was different from other groups. The pharmacokinetic studies showed that the Cmax, Tmax, AUC, t1/2, and MRT of the major compounds of different extracted parts were significantly different in rat plasma at same dosage. Emodin-O-hex-sulfate, tetrahydroxystilbene-O-(galloyl)-hex, emodin (original and generated through EDG deglycosylation), and other free anthraquinones might be responsible for the hepatotoxicity of PM in vivo. PM extracts produced inhibitory effects on drug metabolic enzymes, include CYP3A4, CYP2C19, CYP2E1, UGT1A1, etc. And these effects may be related to its hepatotoxicity and pharmacokinetic behavior different. This information on hepatotoxicity and the pharmacokinetic comparison may be useful to understand the toxicological effects of PM.

【 授权许可】

Unknown