Effect of Kansui Radix and Glycyrrhizae Radix et Rhizoma in Gansui Banxiatang on CYP450 Enzyme in Ascites Rats
10.13422/j.cnki.syfjx.20221428
- VernacularTitle:甘遂半夏汤中甘遂甘草反药组合加减应用对腹水大鼠CYP450酶的影响
- Author:
Jia HE
1
;
Min HUO
1
;
Shaohong CHEN
1
;
Linlin XIU
1
;
Wei LI
1
;
Xu WANG
1
;
Na LI
1
;
Haiyan LIU
1
;
Gansheng ZHONG
1
Author Information
1. Beijing University of Chinese Medicine, Beijing 100029, China
- Publication Type:Journal Article
- Keywords:
eighteen antagonisms;
Gansui Banxiatang;
Kansui Radix;
Glycyrrhizae Radix et Rhizoma;
cytochrome P450
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(23):10-18
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the relationship between Kansui Radix and Glycyrrhizae Radix et Rhizoma in the Gansui Banxiatang based on cytochrome P450 (CYP450) enzyme and ascites rats. MethodA total of 150 Wistar rats were randomized into blank group (distilled water, ig), model group (distilled water, ig), Gansui Banxiatang group (5.68 g·kg-1·d-1, ig), Gansui Banxiatang without Kansui Radix group (5.57 g·kg-1·d-1, ig), Gansui Banxiatang without Glycyrrhizae Radix et Rhizoma group (4.01 g·kg-1·d-1, ig), and Gansui Banxiatang without Kansui Radix And Glycyrrhizae Radix et Rhizoma group (3.90 g·kg-1·d-1, ig), with 25 rats in each group. The Gansui Banxiatang was composed of 1.1 g Kansui Radix, 9 g Pinelliae Rhizoma Praeparatum, 15 g Paeoniae Radix Alba, 16.7 g Glycyrrhizae Radix et Rhizoma praeparata cum melle, and 15 g honey. The rats, except for the blank group, were injected (ip) with Walker-256 cells to induce cancerous ascites. The administration lasted 7 days for each group. The concentration of probe drugs was detected by high performance liquid chromatography (HPLC) and based on the metabolic rates of the drugs, the CYP450 enzyme activity was yielded. The CYP450 enzyme gene expression was determined by Real-time PCR, and CYP450 enzyme protein expression by Western blot. ResultCompared with the blank group, the model group showed high activity of CYP1A2 and CYP2C9, low activity of CYP2E1, CYP2C19, and CYP3A4, low mRNA expression of CYP2E1, CYP2C19, CYP2C9, and CYP3A4, and low protein expression of CYP2E1 and CYP3A4 (P<0.05). Compared with the model group, Gansui Banxiatang group displayed low activity of CYP2C9 and high expression of CYP3A4 mRNA (P<0.01), and Gansui Banxiatang without Kansui Radix group demonstrated low activity of CYP1A2, high activity of CYP2E1 and CYP3A4, high mRNA expression of CYP1A2, CYP2E1, CYP2C19, and CYP3A4, and high protein expression of CYP2E1 and CYP3A4 (P<0.05). In comparison with the model group, the Gansui Banxiatang without Glycyrrhizae Radix Et Rhizoma group showed low activity of CYP2C9, high activity of CYP3A4, and high mRNA expression of CYP2E1 and CYP2C19 (P<0.05), and Gansui Banxiatang without Kansui Radix and Glycyrrhizae Radix Et Rhizoma group had low activity of CYP2C9, high activity of CYP3A4, and high CYP3A4 mRNA expression (P<0.01). The activity of CYP2E1, CYP2C9, and CYP3A4 was higher, and the mRNA expression of CYP1A2, CYP2C19, and CYP3A4 and CYP3A4 protein expression were higher in the Gansui Banxiatang without Kansui Radix group than in the Gansui Banxiatang group (P<0.05). The activity of CYP2C9 and CYP3A4, and CYP2C19 mRNA were higher and mRNA expression of CYP3A4 was lower in the Gansui Banxiatang without Glycyrrhizae Radix Et Rhizoma group than in the Gansui Banxiatang group (P<0.05). The activity of CYP2C9 and CYP3A4 in the Gansui Banxiatang without Kansui Radix and Glycyrrhizae Radix et Rhizoma group was higher than that in the Gansui Banxiatang group (P<0.01). ConclusionThe four prescriptions all showed certain efficacy in the perspective of CYP450 enzyme, among which Gansui Banxiatang without Kansui Radix had the best effect and was better than Gansui Banxiatang. The Kansui Radix and Glycyrrhizae Radix et Rhizoma did not show antagonism in Gansui Banxiatang, but reduced the effect. Thus, in this study, the medicinal pair may show mutual inhibition.