@article{uoadl:3021408,
    volume = "26",
    number = "32",
    pages = "5982-6015",
    journal = "Current Medicinal Chemistry",
    issn = "0929-8673",
    keywords = "activator protein 1 transcription factor;  alkaloid;  berberine;  endothelial nitric oxide synthase;  evodiamine;  glucose transporter 2;  glycogen synthase kinase;  glycogen synthase kinase 3;  growth factor receptor bound protein 2;  insulin receptor substrate 1;  liver kinase B1;  mammalian target of rapamycin complex 1;  mitogen activated protein kinase 1;  mitogen activated protein kinase 3;  mitogen activated protein kinase kinase 1;  myeloid differentiation factor 88;  neferine;  oxymatrine;  piperine;  proline rich protein 5;  protein kinase C zeta;  pyruvate dehydrogenase;  Ras protein;  Rheb protein;  SOS protein;  transcription factor FOXO;  transforming growth factor beta activated kinase 1;  trigonelline;  tumor necrosis factor receptor;  unclassified drug;  alkaloid;  antidiabetic agent;  biological product;  insulin, cell growth;  cell survival;  diabetes mellitus;  genetic transcription;  glucose oxidation;  glucose tolerance;  impaired glucose tolerance;  inflammation;  insulin dependent diabetes mellitus;  insulin release;  insulin resistance;  lipotoxicity;  morbidity;  non insulin dependent diabetes mellitus;  oxidative stress;  phenotype;  Pi3K/Akt signaling;  prevalence;  protein expression;  protein synthesis;  Review;  animal;  chemistry;  diabetes mellitus;  drug effect;  human;  metabolism;  pancreas islet beta cell;  pathology, Alkaloids;  Animals;  Biological Products;  Diabetes Mellitus;  Humans;  Hypoglycemic Agents;  Insulin;  Insulin Resistance;  Insulin-Secreting Cells",
    BIBTEX_ENTRY = "article",
    year = "2019",
    author = "Christodoulou, M.-I. and Tchoumtchoua, J. and Skaltsounis, A.-L. and Scorilas, A. and Halabalaki, M.",
    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 in-depth 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. © 2019 Bentham Science Publishers",
    title = "Natural alkaloids intervening the insulin pathway: New hopes for anti-diabetic agents?",
    doi = "10.2174/0929867325666180430152618"
}