Effects of Aconitum carmichaelii Water Extract on the Expression of Efflux Transporters and Tight Junction Proteins in Duo- denum of Rats
- VernacularTitle:附子水提物对大鼠十二指肠外排转运蛋白和紧密连接蛋白表达的影响
- Author:
Miaomiao JI
1
;
Xinli LIANG
1
;
Youbao ZHONG
2
;
Lai CHEN
2
;
Zhenggen LIAO
1
Author Information
1. Key Laboratory of Modern Preparation of Chinese Meteria Medica,Ministry of Education,Jiangxi University of TCM,Nanchang 330004,China
2. Laboratory Animal Research Center for Science and Technology,Jiangxi University of TCM,Nanchang 330004,China
- Publication Type:Journal Article
- Keywords:
Aconitum carmichaelii;
Water extract;
Duodenum;
Efflux transporter;
Tight junction protein;
Cell bypass pathway;
Drug interaction;
Rat
- From:
China Pharmacy
2019;30(20):2813-2817
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: To study the effects of Aconitum carmichaelii water extract on the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins as well as their genes in duodenum tissues of rats. METHODS: Thirty-two SD male rats were randomly divided into normal group, A. carmichaelii water extract low-dose, medium-dose and high-dose groups [0.45, 0.9, 1.8 g/(kg·d), by crude drug], with 8 rats in each group. They were given water and relevant liquid 0.1 mL/kg intragastrically for consecutive 7 d. After last administration, the duodenal segments of rats were collected. Western blotting assay was used to detect the expression of efflux transporters as P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), multidrug resistance protein 2 (Mrp2) as well as tight junction proteins as Claudin-1, Occludin and ZO-1. mRNA expression of 6 kinds of proteins relevant gene were determined by qRT-PCR respectively. RESULTS: Compared with normal group, the protein expression of P-gp, Mrp2, Bcrp, Claudin-1, Occludin and ZO-1 in duodenum of rats were increased significantly in A. carmichaelii water extract groups (P<0.01). mRNA expression of P-gp in A. carmichaelii water extract groups, mRNA expression of Bcrp in A. carmichaelii water extract low-dose and high-dose groups as well as mRNA expression of Claudin-1 in A. carmichaelli water extract medium-dose and high-dose groups were increased significantly, with statistical significance (P<0.05 or P<0.01). There was no statistical significance in mRNA expression of other genes (P>0.05). CONCLUSIONS: A. carmichaelii water extract can up-regulate the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins at the level of mRNA and/or protein, thus may interact with other substrates of the aforementioned efflux transporters and drugs with cell bypass pathway as the main transport pathway. In clinical practice, adjustment of dosage may be considered in drug combination.