Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair.

Phytochemical investigation of the stem bark of Myristica fatua Houtt. led to the isolation of a new compound 1 (3-tridecanoylbenzoic acid), along with six known acylphenols (2-7). All the compounds displayed moderate inhibitory activity on α-amylase and significant activity on α-glucosidase; however malabaricone B (6) and C (7) were identified as potent α-glucosidase inhibitors with IC50 values of 63.70 ± 0.546, and 43.61 ± 0.620 µM respectively. Acylphenols (compounds 3-7) also showed significant antiglycation property. The molecular docking and dynamics simulation studies confirmed the efficient binding of malabaricone C with C-terminus of human maltase-glucoamylase (2QMJ). Malabaricone B also enhanced the 2-NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy glucose] uptake in L6 myotubes. These findings demonstrate that acylphenols isolated from Myristica fatua Houtt. can be considered as a lead scaffold for the treatment of type II diabetes mellitus.

[1]  M. Doble,et al.  Interaction of cinnamic acid derivatives with commercial hypoglycemic drugs on 2-deoxyglucose uptake in 3T3-L1 adipocytes. , 2011, Journal of agricultural and food chemistry.

[2]  G. Bai,et al.  Structural insight into substrate specificity of human intestinal maltase-glucoamylase , 2011, Protein & Cell.

[3]  I. G. Shibi,et al.  Comparison of antidiabetic potential of (+) and (−)-hopeaphenol, a pair of enantiomers isolated from Ampelocissus indica (L.) and Vateria indica Linn., with respect to inhibition of digestive enzymes and induction of glucose uptake in L6 myotubes , 2016 .

[4]  E. Gulve,et al.  Chemistry and biochemistry of type 2 diabetes. , 2004, Chemical reviews.

[5]  G. Go,et al.  Promotion of Glucose Uptake in C2C12 Myotubes by Cereal Flavone Tricin and Its Underlying Molecular Mechanism. , 2017, Journal of agricultural and food chemistry.

[6]  J. Desrivot,et al.  Antiparasitic activity of some New Caledonian medicinal plants. , 2007, Journal of ethnopharmacology.

[7]  K. Raghu,et al.  Studies on α-glucosidase, aldose reductase and glycation inhibitory properties of sesquiterpenes and flavonoids of Zingiber zerumbet Smith , 2015, Natural product research.

[8]  S. Withers,et al.  Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. , 2012, Journal of medicinal chemistry.

[9]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[10]  J. M. Petrash,et al.  Characterization of Emodin as a Therapeutic Agent for Diabetic Cataract. , 2016, Journal of natural products.

[11]  A. Fournet,et al.  Screening of some New Caledonian and Vanuatu medicinal plants for antimycobacterial activity. , 2005, Journal of ethnopharmacology.

[12]  A. Llebaria,et al.  A prospect for pyrrolidine iminosugars as antidiabetic α-glucosidase inhibitors. , 2012, Journal of medicinal chemistry.

[13]  R. Somwar,et al.  Stimulation of glucose and amino acid transport and activation of the insulin signaling pathways by insulin lispro in L6 skeletal muscle cells. , 1998, Clinical therapeutics.

[14]  Weibiao Zhou,et al.  In vitro and in silico studies of the inhibition activity of anthocyanins against porcine pancreatic α-amylase , 2016 .

[15]  J. D. Connolly,et al.  Malabaricones A--D, novel diarylnonanoids from Myristica malabarica Lam (Myristicaceae). , 1977, Journal of the Chemical Society. Perkin transactions 1.

[16]  R. Storms,et al.  A quantitative starch-iodine method for measuring alpha-amylase and glucoamylase activities. , 2006, Analytical biochemistry.

[17]  J. Senior,et al.  Drug-related hepatotoxicity. , 2006, The New England journal of medicine.

[18]  Y. Kraan,et al.  Mechanistic insights in glycation-induced protein aggregation. , 2014, Biomacromolecules.

[19]  K. Shetty,et al.  Inhibitory potential of herb, fruit, and fungal-enriched cheese against key enzymes linked to type 2 diabetes and hypertension , 2007 .

[20]  P. Yadav,et al.  Pongamol from Pongamia pinnata stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells , 2011, Molecular and Cellular Endocrinology.

[21]  M. Megawati,et al.  Resorcinol Compounds Isolated form the Bark of Myristica fatua Houtt. , 2017 .

[22]  B. Nichols,et al.  Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. , 2008, Journal of molecular biology.

[23]  S. Nissen,et al.  Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. , 2007, The New England journal of medicine.

[24]  R. Pandey,et al.  Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and their in vitro antiproliferative activity. , 2016, Food chemistry.

[25]  Eisuke Kato,et al.  α-Amylase inhibitory triterpene from Abrus precatorius leaves. , 2014, Journal of agricultural and food chemistry.

[26]  Asim Muhammad,et al.  Antidiabetic compounds from Sarracenia purpurea used traditionally by the Eeyou Istchee Cree First Nation. , 2012, Journal of natural products.

[27]  Hua Sun,et al.  Natural Prenylchalconaringenins and Prenylnaringenins as Antidiabetic Agents: α-Glucosidase and α-Amylase Inhibition and in Vivo Antihyperglycemic and Antihyperlipidemic Effects. , 2017, Journal of agricultural and food chemistry.

[28]  Om P. S. Patel,et al.  Naturally Occurring Carbazole Alkaloids from Murraya koenigii as Potential Antidiabetic Agents. , 2016, Journal of natural products.

[29]  M. Litaudon,et al.  A potent alpha-glucosidase inhibitor from Myristica cinnamomea King. , 2016, Phytochemistry.

[30]  P. Castilho,et al.  Evaluation of Asteraceae herbal extracts in the management of diabetes and obesity. Contribution of caffeoylquinic acids on the inhibition of digestive enzymes activity and formation of advanced glycation end-products (in vitro). , 2017, Phytochemistry.

[31]  V. Karunaratne,et al.  Arylalkanones from Myristica dactyloides , 1988 .

[32]  P. Hollander,et al.  Anti-Diabetes and Anti-Obesity Medications: Effects on Weight in People With Diabetes , 2007 .

[33]  M. Hanafi,et al.  New cytotoxic compounds from Myristica fatua Houtt leaves against MCF-7 cell lines , 2017 .