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

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.

• Authors: Maria-Ioanna Christodoulou, Job Tchoumtchoua, Alexios-Leandros Skaltsounis, Andreas Scorilas, Maria Halabalaki
• Journal: Current medicinal chemistry (Curr Med Chem) Vol. 26 Issue 32 Pg. 5982-6015 ( 2019) ISSN: 1875-533X [Electronic] United Arab Emirates
• PMID: 29714135 (Publication Type: Journal Article, Review)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Alkaloids
• Biological Products
• Hypoglycemic Agents
• Insulin

Topics

• Alkaloids (chemistry, pharmacology)
• Animals
• Biological Products (chemistry, pharmacology)
• Diabetes Mellitus (drug therapy, metabolism, pathology)
• Humans
• Hypoglycemic Agents (chemistry, pharmacology)
• Insulin (metabolism)
• Insulin Resistance
• Insulin-Secreting Cells (drug effects, metabolism)