Effects of Vitexin on the Pharmacokinetics and mRNA Expression of CYP Isozymes in Rats

Abstract

In traditional therapy with Chinese medicine, vitexin has several pharmacological properties, including antinociceptive, antispasmodic, antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. Recently, vitexin was shown to protect the heart against ischemia/reperfusion injury in an in vitro model by inhibiting apoptosis. The purpose of this study was to find out whether vitexin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (10 mg/kg), tolbutamide (1 mg/kg), and midazolam (5 mg/kg), was given as oral administration to rats treated with short or long period of intravenous vitexin via the caudal vein. Blood samples were collected at a series of time points, and the concentrations of probe drugs in plasma were determined by HPLC-mass spectrometry (MS)/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time reverse transcription-polymerase chain reaction was performed to determine the effects of vitexin on the mRNA expression of CYP1A2, CYP2C11, and CYP3A1 in rat liver. Treatment with short or long period of vitexin had no effects on rat CYP1A2. However, CYP3A1 enzyme activity was inhibited by vitexin in a concentration-dependent and time-dependent manner. Furthermore, CYP2C11 enzyme activity was induced after short period treatment but inhibited after long period of vitexin treatment. The mRNA expression results were in accordance with the pharmacokinetic results. In conclusion, vitexin can either inhibit or induce activities of CYP2C11 and CYP3A1. Therefore, caution is needed when vitexin is co-administered with some CYP2C11 or CYP3A1 substrates in clinic, which may result in treatment failure and herb-drug interactions.

Inclusion of vitexin in β-cyclodextrin: preparation, characterization and expectorant/antitussive activities

“…Recently, it has been demonstrated that vitexin (0.2, 1 and 5 mg/kg) inhibits inflammation in allergic asthma induced by ovalbumin [14]. However, a study of the metabolism of vitexin in rats showed that it is poorly absorbed in the gastrointestinal tract [15] and has low bioavailability [16,17]. Once that is probably due to the low solubility in water (7.62 μg/mL), it is important to develop methodologies improving the solubility of vitexin in aqueous medium so that its therapeutic action is improved.…”

Vitexin attenuates acute doxorubicin cardiotoxicity in rats via the suppression of oxidative stress, inflammation and apoptosis and the activation of FOXO3a

“…Hawthorn, of the rosaceae plant family, is a traditional Chinese medicine that is used to promote digestion (14). It has been reported that the ketone compounds extracted from the Hawthorn leaves are able to regulate blood lipids, blood pressure, increase coronary flow and protect the ischemic myocardium (15)(16)(17). Vitexin is the active ingredient extracted from hawthorn leaves, and it has previously been demonstrated that vitexin has a protective effect against hypoxia in the reoxygenation of myocardial cells (18).…”

Two Approaches for Evaluating the Effects of Galangin on the Activities and mRNA Expression of Seven CYP450

“…In the human body, the main CYP enzymes involved in drug metabolism include CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP2E1, among which CYP2C9, CYP2D6 and CYP3A4 account for approximately 50% of the total liver CYP enzyme levels and can metabolize nearly 80% of all clinical drugs [16]. Human CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP2E1 share high homology with rat CYP1A2, CYP2B3, CYP2C11, CYP2C13, CYP2D4, CYP3A1 and CYP2E1, respectively [17]. CYP1A2 is mainly distributed in the liver, accounting for 13% of the total CYP450.…”