Identification of Potential Plant-Derived Pancreatic Beta-Cell-Directed Agents Using New Custom-Designed Screening Method: Gymnema sylvestre as an Example.

ABSTRACT

BACKGROUND: Folk medicines are attractive therapeutic agents for treating type 2 diabetes mellitus (T2DM). Most plant extracts that have been suggested to restore ß-cells function were tested in vivo. Some only have been tested in vitro to determine whether they have a direct effect on ß-cells islets of Langerhans. Currently, there are no defined criteria for screening of ß-cell-directed plant-based remedies as potential antidiabetic agents. SUMMARY: In this review, we have identified certain criteria/characteristics that can be used to generate a "screening portfolio" to identify plant extracts as potential ß-cell-directed agents for the treatment of T2DM. To validate our screening method, we studied the potential therapeutic efficacy of a Gymnema sylvestre (GS) extract using the screening criteria detailed in the review. Six criteria have been identified and validated using OSA®, a GS extract. By using this screening method, we show that OSA® fulfilled most of the criteria identified for an effective ß-cell-directed antidiabetic therapy, being an effective insulin-releasing agent at nontoxic concentrations; maintaining ß-cell insulin content by stimulating a concomitant increase in insulin gene transcription; maintaining ß-cell mass by protecting against apoptosis; and being effective at maintaining normoglycemia in vivo in a mouse model and a human cohort with T2DM. KEY MESSAGES The present review has highlighted the importance of having a screening portfolio for plant extracts that have potential antidiabetic effects in the treatment of T2DM. We propose that this screening method should be adopted for future studies to identify new ß-cell-directed antidiabetic plant derived agents.