In vivo effect of arecoline hydrobromide on rat hepatic CYP2B expression and its mechanism / 中草药

Objective: To study the effect of arecoline hydrobromide (AH) on rat hepatic CYP2B expression/activity, as well as the underlying regulation mechanism in vivo. Methods: After oral administration of AH (4, 20, and 100 mg/kg/d) to rats for 7 consecutive days, the hepatic CYP2B activity was detected by LC-MS/MS method, the protein levels of hepatic CYP2B, total CAR, and endonuclear CAR were detected by Western blotting, and the hepatic CYP2B1 mRNA level was detected by real-time PCR. Results: AH treatment had no effect on rat hepatic CYP2B protein level, but the hepatic CYP2B1 mRNA level was dose-dependently increased. Additionally, although the hepatic CYP2B activity was induced by AH treatment, the induction was weakened with the dose increase of AH. Furthermore, the protein content of hepatic endonuclear CAR was increased while the total CAR protein remained unchanged following AH treatment. Conclusion: AH induces rat hepatic CYP2B by promoting nuclear translocation of CAR. The regulation of AH on rat hepatic CYP2B largely involve transcriptional activation of the gene, partially involve the post-translational modification of CYP2B protein. Our results also suggest that the risk of metabolic interaction could be existed when the substrate drugs of CYP2B are administered in betel-quid used human.

Induction of rat hepatic CYP2E1 expression by arecoline in vivo / 药学学报

The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg·kg-1·d-1) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepatic CYP2El does not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- translational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human.

Induction of rat hepatic CYP2E1 expression by arecoline in vivo / 药学学报

The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg x kg(-1) x d(-1)) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepaticdoes not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- ranslational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human.