Study on the liver and kidney toxicity and effective substances of rhubarb anthraquinone
10.13699/j.cnki.1001-6821.2018.10.022
- VernacularTitle:大黄蒽醌类成分肝肾毒性和效应物质研究
- Author:
Zhi-Hua DOU
1
;
Bo XU
;
Zhong SHI
;
Chen-Ping WANG
;
Dong-Ping XUAN
Author Information
1. 南通大学附属南通第三医院药学部
- Keywords:
rhubarb;
anthraquinone;
serum containing drug;
serum pharmacology;
serum pharmacochemistry;
hepatic and renal toxicity;
effective substance
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(10):1214-1217
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the liver and kidney toxicity and effective substances of rhubarb anthraquinone.Methods Rat serums containing drugs (SCDs) were prepared after intragastric administration of the rhubarb extract of free anthraquinones.The toxicity of different doses of SCDs on HL-7702 and HK-2 cells were investigated using the method of serum pharmacology with aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) leakage as the indexes.Using the serum pharmacochemistry method,the chromatogram of SCDs was detected by HPLC,and the UV absorption spectrograms of peaks were extracted.Comparing the chromatogram of SCDs with that of blank serum,drug-induced constituents in blood were analyzed.By comparing the chromatograms and spectrograms with those of extracts and reference substances,the sources of the drug-induced components were analyzed and some constituents were identified.Results Compared with the cells of corresponding blank serum groups,the leakage of AST in HL-7702 cells significantly increased in 100％ and 80％ SCDs groups [(160.67 ± 19.35)U · L-1 vs (113.33 ± 2.08) U · L-1,(123.00 ± 7.00) U · L-1 vs (82.33 ± 11.93) U · L-1],the differences were statistically significant (all P ＜0.01),and the leakage LDH in HK-2 cells significantly increased in 100％,80％ and 40％ SCDs groups [(644.33 ±9.29)U · L-1vs (606.67 ± 11.85)U · L-1,(624.33 ±34.95)U · L-1 vs (504.33 ± 16.04)U · L-1,(603.67 ±42.83)U · L-1vs (398.00 ± 19.08)U · L-1],the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01).Twenty drug-induced components were detected in rat serum after intragastric administration of the rhubarb extract of free anthraquinones,five of them were the original free anthraquinones and fifteen were metabolites.Five original free anthraquinones were identified as aloe emodin,rhein,emodin,chrysophanol,and physcion.Eight constituents out of 15 metabolites were identified as aloe emodin-8-O-glucopyranoside,rhein -8-O-glucopyranoside,emodin-1-O-glucopyranoside,chrysophanol-1-0-glucopyranoside,chrysophanol -8-O-glucopyranoside,emodin-8-O-glucopyranoside,aloe emodin-3-CH2-O-glucopyranoside,and physcion-8-O-glucopyranoside.Other 7 metabolites possessed the same ultraviolet absorption character as that of anthraquinones.Conclusion Anthraquinones in rhubarb have liver and kidney toxicity,and the effective substances are conjugated anthraquinone produced in vivo metabolism and free anthraquinone in vitro.
