Natural Alkaloids Intervening the Insulin Pathway: New Hopes for Anti-Diabetic Agents?

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Author(s): Maria-Ioanna Christodoulou*, Job Tchoumtchoua , Alexios-Leandros Skaltsounis , Andreas Scorilas, Maria Halabalaki .

Journal Name: Current Medicinal Chemistry

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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 support 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.

Keywords: Alkaloids, natural products, diabetes mellitus (DM), insulin-signaling pathway, insulin resistance, inflammation, oxidative stress.

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(E-pub Ahead of Print)
DOI: 10.2174/0929867325666180430152618
Price: $95

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