Title:Natural Alkaloids Intervening the Insulin Pathway: New Hopes for Anti-Diabetic Agents?
VOLUME: 26 ISSUE: 32
Author(s):Maria-Ioanna Christodoulou*, Job Tchoumtchoua , Alexios-Leandros Skaltsounis , Andreas Scorilas and Maria Halabalaki
Affiliation:Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Panepistimioupoli Zografou 15771, Athens, Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli Zografou 15771, Athens, Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli Zografou 15771, Athens, Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Panepistimioupoli Zografou 15771, Athens, Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli Zografou 15771, Athens
Keywords:Alkaloids, natural products, diabetes mellitus (DM), insulin-signaling pathway, insulin resistance, inflammation,
oxidative stress.
Abstract: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.
