School of Biomedical Sciences, Ulster University, Coleraine, Co. Londonderry, Northern Ireland, United Kingdom.
Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Dhaka, Bangladesh.
PLoS One. 2022 Mar 3;17(3):e0264632. doi: 10.1371/journal.pone.0264632. eCollection 2022.
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.
在民间传说中，海桑（H. fomes）被广泛用于治疗各种疾病，如糖尿病、心脏和肝脏疾病。本研究旨在阐明海桑热水提取物（HWHF）的抗糖尿病作用，包括对 BRIN BD11 细胞和分离的小鼠胰岛胰岛素释放以及高脂肪喂养大鼠葡萄糖稳态的影响。还评估了抗糖尿病活性的分子机制以及活性化合物的分离。非毒性浓度的 HWHF 刺激分离的小鼠胰岛和克隆胰腺β细胞的浓度依赖性胰岛素释放。该刺激作用在葡萄糖和异丁基甲基黄嘌呤（IBMX）存在下增强，在甲苯磺丁脲或去极化浓度 KCl 的存在下持续存在，但被胰岛素释放的既定抑制剂如二氮嗪、维拉帕米和 Ca2+螯合剂减弱。HWHF 导致β-细胞膜去极化并增加细胞内 Ca2+。该提取物还增强了 3T3-L1 分化的脂肪细胞中的葡萄糖摄取和胰岛素作用，并以剂量依赖性方式显著抑制体外淀粉消化、蛋白质糖基化、DPP-IV 酶活性和葡萄糖扩散。HWHF（250 mg/5ml/kg b.w.）口服给予高脂肪喂养大鼠可显著改善葡萄糖耐量和血浆胰岛素反应，并抑制血浆 DPP-IV 活性。HWHF 还降低了体内葡萄糖吸收和肠双糖酶活性，同时增加了胃肠道蠕动和未吸收蔗糖的转运。从 HWHF 中分离出与槲皮素（C21 H20 O11）分子量相似的化合物，其分子量范围为 447.9 至 449.9 Da，可在体外刺激胰岛素释放，并改善小鼠的葡萄糖耐量和血浆胰岛素反应。总之，海桑及其水溶性植物化学物质如槲皮素可能通过多种机制发挥抗糖尿病作用，这些机制可能作为 2 型糖尿病管理的饮食辅助手段有用。
