Study on Interaction of Cytochrome P450 CYP450 with an Anti Daibetic Herb

Abstract

Diabetes mellitus (DM) is a chronic disease and its prevalence has been increasing globally. It is linked with comorbid diseases such as heart diseases, stroke, kidney diseases, diabetic retinopathy and also related to cancer. Hence, concomitant uses of drugs increases and leads towards the risk of side or adverse effects. Therefore necessity of additional drugs to manage DM and DM related risks with fewer side effects. Herbal medicinal products are gaining global popularity and acceptability because of the arguable belief that all herbal products are safe and nontoxic. In Ayurveda, Gymnema sylvestre R.Br. (G. sylvestre) is a well-known Indian traditional herb to treat DM. Accompanied by various other phyto-constituents present in the G. sylvestre, the group of gymnemic acids (GA) are main bioactive phyto-constituents responsible for the anti-diabetic activity. Owing to these bioactive phyto-constituents reported to have numerous pharmacological activities, G. sylvestre is often traditionally used in conjunction with other allopathic drug to cure DM and DM linked diseases. Hence, herb drug interactions (HDI) that are a consequence of this polytherapy demands significant attention in clinical practice, as concurrent use of herbs may mimic, magnify, or oppose the effect of prescribed drugs. Many HDI are due to alteration in metabolic activities of drug metabolizing enzymes Cytochrome P450 (CYP). Inhibition and induction of these CYP450 enzymes activities results in the serious and adverse HDI at metabolic level. However, there are no reports on total GA enriched fraction (triterpenoids enriched fraction) from G. sylvestre and their interaction with CYP450. The aim of present research work was to evaluate the interaction potential of G. sylvestre with CYP3A4, CYP2C9, CYP1A2 and CYP2D6 enzymes in rats. newline