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

Background: Folk medicines are attractive therapeutic agents for treating type 2 diabetes mellitus (T2DM). Most plant extracts that have been suggested to restore beta-cells function were tested in vivo. Some only have been tested in vitro to determine whether they have a direct effect on beta-cells islets of Langerhans. Currently, there are no defined criteria for screening of beta-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 beta-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 (R), a GS extract. By using this screening method, we show that OSA (R) fulfilled most of the criteria identified for an effective beta-cell-directed antidiabetic therapy, being an effective insulin-releasing agent at nontoxic concentrations; maintaining beta-cell insulin content by stimulating a concomitant increase in insulin gene transcription; maintaining beta-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 beta-cell-directed antidiabetic plant derived agents.