In folklore, Heritiera fomes (H. fomes) has been extensively used in treatment of various ailments such as diabetes, cardiac and hepatic disorders. The present study aimed to elucidate the antidiabetic actions of hot water extract of H. fomes (HWHF), including effects on insulin release from BRIN BD11 cells and isolated mouse islets as well as glucose homeostasis in high-fat-fed rats. Molecular mechanisms underlying anti-diabetic activity along with isolation of active compounds were also evaluated. Non-toxic concentrations of HWHF stimulated concentration-dependent insulin release from isolated mouse islets and clonal pancreatic β-cells. The stimulatory effect was potentiated by glucose and isobutyl methylxanthine (IBMX), persisted in presence of tolbutamide or a depolarizing concentration of KCl but was attenuated by established inhibitors of insulin release such as diazoxide, verapamil, and Ca2+ chelation. HWHF caused depolarization of the β-cell membrane and increased intracellular Ca2+. The extract also enhanced glucose uptake and insulin action in 3T3-L1 differentiated adipocytes cells and significantly inhibited in a dose-dependent manner starch digestion, protein glycation, DPP-IV enzyme activity, and glucose diffusion in vitro. Oral administration of HWHF (250 mg/5ml/kg b.w.) to high-fat fed rats significantly improved glucose tolerance and plasma insulin responses and it inhibited plasma DPP-IV activity. HWHF also decreased in vivo glucose absorption and intestinal disaccharidase activity while increasing gastrointestinal motility and unabsorbed sucrose transit. Compounds were isolated from HWHF with similar molecular weights to quercitrin (C21 H20 O11) ranging from 447.9 to 449.9 Da which stimulated the insulin release in vitro and improved both glucose tolerance and plasma insulin responses in mice. In conclusion, H. fomes and its water-soluble phytochemicals such as quercitrin may exert antidiabetic actions mediated through a variety of mechanisms which might be useful as dietary adjunct in the management of type 2 diabetes.
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