Effects of tetrahydroxystilbene glucoside on mouse liver cytochrome P450 enzyme expressions

Abstract

1. To investigate the effects of tetrahydroxystilbene glucoside (TSG), the main active component of Polygonum multiflorum, on mouse liver cytochrome P450 (Cyp) enzyme protein expressions. Male mice were randomly divided into the control, TSG low (10 mg/kg) and high dose (40 mg/kg) groups. After TSG intragastrical administration for 3, 5 and 7 d, mice were sacrificed and the mouse body and liver weight were detected. The Cyp enzymes and various transcription factors such as AhR, PXR and PPARα protein expressions in mouse livers were measured by Western blotting assay. 2. No significant difference of mouse body and liver weight between the control and TSG treatment groups was detected. Additionally, TSG decreased Cyp1a2 and Cyp2e1 protein expressions after TSG treatment for 3, 5 and 7 d, respectively. Moreover, TSG suppressed Cyp3a11 protein expression after TSG treatment for 5 and 7 d. Furthermore, TSG high dose inhibited AhR and PXR protein expressions after TSG treatment for 5 and 7 d, while both TSG low dose and high dose obviously decreased PPARα protein level from TSG treatment for 3 d. 3. TSG has inhibitory effects on mouse liver Cyp1a2, Cyp2e1 and Cyp3a11 protein expressions through the suppression of AhR, PXR and PPARα activation.

In Vivo Toxicity of Solasonine and Its Effects on cyp450 Family Gene Expression in the Livers of Male Mice from Four Strains

“…Moreover, GH and insulin-like growth factor-1 (IGF-1) levels after exercise depended on the work done, and the relative levels of CYP1A2 expression correlated with the time and the amount of work done by athletes [40]. However, tetrahydroxystilbene glucoside (TSG), the main active component of Polygonum multiflorum , has inhibitory effects on mouse liver CYP1A2, CYP2E1, and CYP3A11 protein expression through the suppression of aryl hydrocarbon receptor (AhR), pregnenolone X receptor (PXR), and proliferate-activated receptor α (PPARα) activation [19]. In addition, liver insufficiency also impairs CYP450 enzymes’ expression.…”

“…Members of the cyp450 gene family are usually expressed at various levels. For studies on drug biotransformation and function, cyp1a2, cyp2e1, and cyp3a11, which are expressed at high levels in human and murine livers, are often employed [9,17,18,19]. Of note, basal levels of the expression of genes in the cyp450 family were reported to be dependent on factors such as gender [17,18], diseases [20], stresses [21], or age [22].…”

Screening for biomarkers of liver injury induced by Polygonum multiflorum: a targeted metabolomic study

“…BAs were derived from the catabolism of cholesterol, and BAs pool could be divided into primary and secondary BAs based on biological source. In the progress of primary BAs biosynthesis, P450 enzymes including CYP7A1, CYP8B1, CYP27A1, and CYP7B1 were involved in de Aguiar Vallim et al (2013), and there has been literatures reporting that HSW and anthraquinones in it would inhibit P450s involved in metabolism of pharmaceuticals (Sridhar et al, 2012; Wang et al, 2015). However, there was little study focusing on the influence of HSW to P450s involved in primary BAs biosynthesis in pathogenesis of liver injury.…”

Advances in the Study of the Potential Hepatotoxic Components and Mechanism of Polygonum multiflorum

“…The alcoholic extract of PM inhibited the activity of CYP2C19 and CYP2C9, and the aqueous extract of PM inhibited the activity of CYP2C19, CYP2C9, CYP2B6, CYP2D6, and CYP1A2 [ 92 , 93 ]. TSG has inhibitory effects on mouse liver CYP1A2, CYP2E1, and CYP3A11 protein expression through the suppression of AhR, PXR, and PPAR α activation [ 94 ]. CYP1A2, 2C19, and 2E1 have been reported as the main CYP450s which participated in phase I metabolism of AQs such as emodin [ 92 , 95 ].…”