Effect of Colebrookea oppositifolia Leaf Extracts on Cytochrome P450 and Glutathione S-Transferase Activity in Rats
Effect of Colebrookea oppositifolia Leaf Extracts on Cytochrome P450 and Glutathione S-Transferase Activity in Rats
Rukhsana Anwar1*, Ammara Abd-Us-Sattar1, Afifa Noor2, Kanwal Ashiq1,3 and Shah Jahan4
ABSTRACT
Colebrookea oppositifolia is a medicinal plant that contains many therapeutic constituents. Till now, research has not been conducted related to this plant’s effect on hepatic drug-metabolizing enzymes and glutathion S-transferase. For this purpose, different cytochrome (CYP450) modulators were selected to determine pharmacokinetic interactions. Cimetidine, rifampicin, dexamethasone, and tamoxifen were selected as CYP450 modulators. In a sub-acute in vivo study, 200 mg/kg BW of both extracts were orally administered once daily for 19 days to different groups of rats. CYP modulators were administered to respective groups for last 5 consecutive days. Real-time PCR analysis of hepatic CYP450 subtypes, CYP1A2, CYP2C9, and CYP3A4 was carried out. Moreover, phase II drug-metabolizing enzymes; GST-specific activity, total glutathione, superoxide dismutase, catalase, and malondialdehyde were determined in liver homogenates. The phytochemical analysis of extracts revealed the presence of many important bioactive compounds. Real-time PCR results showed that aqueous extract decreased the mRNA expression of CYP1A2, CYP3A4. The methanolic extract decreased mRNA expression of CYP2C9 and CYP3A4. Both extracts enhanced GST-specific activity, tGSH, SOD, and CAT activity in rats. It is concluded that leaf extracts of C. oppositifolia showed significant interaction with drugs. This can modulate drug-metabolizing enzyme activity and reduce oxidative stress.
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