Background: Accumulating experimental data supports the capacity of natural
compounds to intervene in complicated molecular pathways underlying the pathogenesis of
certain human morbidities. Among them, diabetes is now a world’s epidemic associated with
increased risk of death; thus, the detection of novel anti-diabetic agents and/or adjuvants is of
vital importance. Alkaloids represent a diverse group of natural products with a range of
therapeutic properties; during the last 20 years, published research on their anti-diabetic capacity
has been tremendously increased.
Purpose: To discuss current concepts on the anti-diabetic impact of certain alkaloids, with
special reference to their molecular targets throughout the insulin-signaling pathway.
Methodology: Upon in-depth search in the SCOPUS and PUBMED databases, the literature
on alkaloids with insulin secretion/sensitization properties was critically reviewed.
Results: In-vitro and in-vivo evidence supports the effect of berberine, trigonelline, piperine,
oxymatrine, vindoneline, evodiamine and neferine on insulin-signaling and related cascades
in beta-cells, myocytes, adipocytes, hepatocytes and other cells. Associated receptors, kinases,
hormones and cytokines, are affected in terms of gene transcription, protein expression, activity
and/or phosphorylation. Pathophysiological processes associated with insulin resistance,
beta-cell failure, oxidative stress and inflammation, as well as clinical phenotype are also influenced.
Discussion: Growing evidence suggests the ability of specific alkaloids to intervene in the
insulin-signal transduction pathway, reverse molecular defects resulting in insulin resistance
and glucose intolerance and improve disease complications, in-vitro and in-vivo. Future indepth
molecular studies are expected to elucidate their exact mechanism of action, while large
clinical trials are urgently needed to assess their potential as anti-diabetic agents.