Analysis of Mechanism of Chloroform Extract of Gegen Qinliantang on Alleviating Enterotoxicity Induced by Irinotecan
10.13422/j.cnki.syfjx.20210577
- VernacularTitle:葛根芩连汤三氯甲烷提取物缓解伊立替康所致肠毒性的作用机制分析
- Author:
Yi-han WU
1
;
Yan-fen CHENG
1
;
Di WANG
1
;
Xiao-qin YANG
1
;
Xue-mei ZHONG
1
;
Jie LIN
1
;
Chao-mei FU
1
;
Jin-ming ZHANG
1
;
Yi-chen HU
2
Author Information
1. College of Pharmacy，Chengdu University of Traditional Chinese Medicine，Chengdu 611137，China
2. College of Food and Biological Engineering，Chengdu University，Chengdu 610106，China
- Publication Type:Research Article
- Keywords:
Gegen Qinliantang;
irinotecan hydrochloride （CPT-11）;
enterotoxicity;
oxidative stress;
inflammation;
delayed diarrhea;
loperamide;
tumor
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(16):16-23
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Considering the efficacy of Gegen Qinliantang （GQT） in releasing exterior and clearing interior to alleviate dampness-heat dysentery， we analyzed the mechanism of the chloroform extract of GQT in alleviating enterotoxicity caused by irinotecan to provide an experimental basis for the development of GQT. Method:Kunming mice （n=60） were randomly divided into a blank group， a model group， a loperamide group （positive drug of loperamide hydrochloride capsule， 0.4 mg·kg-1）， and high- （2.3 g·kg-1） and low-dose （1.16 g·kg-1） GQT chloroform extract groups. The mouse model of delayed diarrhea was established by intraperitoneal injection of irinotecan hydrochloride （CPT-11， 55 mg·kg-1） for four consecutive days， meanwhile， the mice in the blank group only received the same volume of normal saline. Corresponding drugs were administered by gavage on the fifth day， respectively， while the ones in the blank group and model group were given distilled water for five consecutive days. The general condition of mice in each group was observed， and diarrhea indexes of mice were recorded. Pathological changes in colon tissues of mice were observed by hematoxylin-eosin （HE） staining. The tumor necrosis factor （TNF）-α， interleukin （IL）-1β， cyclooxygenase （COX）-2， intercellular adhesion molecule （ICAM）-1， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， malondialdehyde （MDA） and nitric oxide （NO） levels in colon tissues were detected with the assay kits. Furthermore， the expression levels of Kelch sample epoxy chloropropane associated protein 1 （Keap1）， nuclear factor E2 related factor 2 （Nrf2）， tight junction protein-1 （ZO-1）， heme oxygenase-1 （HO-1） and tight junction protein （Occludin） were detected by Western blot. Result:Compared with the blank group， the model group showed declined body weight and reduced contents of GSH-Px and SOD （P<0.01）， whereas increased diarrhea indexes and TNF-α， IL-1β， COX-2， ICAM-1， MDA and NO levels （P<0.01）. Abundant inflammatory cells and colonic mucosa with defects， swelling， bleeding， and inflammatory exudation were revealed by HE staining in the mice of the model group. The expression levels of Keap1， Nrf2， ZO-1， HO-1 and Occludin in colon tissues significantly declined （P<0.01）. Compared with the model group， the loperamide group and the high- and low-dose GQT chloroform extract groups exhibited improved weight loss， reduced diarrhea indexes， diminished TNF-α， IL-1β， COX-2， ICAM-1， MDA and NO， and elevated GSH-Px and SOD. HE staining indicated that the cells were compactly arranged with clear nuclei in the high- and low-dose GQT chloroform extract groups， and the expression levels of Keap1， Nrf2， HO-1， Occludin， and ZO-1 were up-regulated. Conclusion:GQT chloroform extract may alleviate CPT-11-induced delayed diarrhea by regulating inflammation and oxidative stress for enhancing the intestinal barrier function. These findings are expected to provide a reference for exploring the toxicity-attenuating effect of Chinese medicinals on chemotherapy drugs and for developing famous classical formulas.
