An integrated multi-target in vitro screening platform to prioritise medicinal plant extracts with antidiabetic activity

Abstract

Medicinal plants have attracted much interest as a potentially inexpensive and culturally acceptable therapy for the treatment of diabetes, however most have not been scientifically evaluated for safety and efficacy. Unfortunately the high cost of clinical studies reside beyond the reach of most academic and research institutions and subsequently do not represent a viable option for exploring the many medicinal plants reported to treat this disease. While animal models afford an accepted alternative, the multifactor nature of diabetes poses a significant challenge as it is not possible to accurately select appropriate animal models without some knowledge of the mechanism through which complex plant extracts elicit their therapeutic effect. To address this problem a multi-target in vitro antidiabetic screening platform was established and used to prioritise plant extracts according to therapeutic target. The selectivity of our screening platform was confirmed through a comparison of known antidiabetic drugs relative to a set of drugs not associated with the treatment of diabetes. Furthermore a selection of natural compounds with previously established in vivo antidiabetic activity highlighted the increased propensity of natural compounds to target multiple molecular mechanisms. Screening of 40 South African medicinal plant extracts identified Sutherlandia frutescens as a promising antidiabetic therapy with a strong lipocentric mechanism. Using a high fat diet induced insulin resistant animal model, we confirmed these antidiabetic properties [1]. Together these findings support an integral role for in vitro assays as a strategy to characterise the antidiabetic potential of natural products prior to confirmation in animal models.