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Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals
Plants ( IF 4.0 ) Pub Date : 2020-10-12 , DOI: 10.3390/plants9101348
Prawej Ansari 1 , Peter R Flatt 1 , Patrick Harriott 1 , Yasser H A Abdel-Wahab 1
Affiliation  

Annona squamosa is generally referred to as a ‘custard apple’. Antidiabetic actions of hot water extract of Annona squamosa (HWAS) leaves together with isolation of active insulinotropic compounds were studied. Insulin release, membrane potential and intracellular Ca2+ were determined using BRIN-BD11 cells and isolated mouse islets. 3T3L1 adipocytes and in vitro models were used to determine cellular glucose uptake, insulin action, starch digestion, glucose diffusion, DPP-IV activity and glycation. Glucose intolerant high-fat fed rats were used for in vivo studies. Active compounds were isolated and characterized by HPLC, LCMS and NMR. HWAS stimulated insulin release from clonal β-cells and mouse islets. Using fluorescent indicator dyes and modulators of insulin secretion, effects could be attributed to depolarization of β-cells and influx of Ca2+. Secretion was stimulated by isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, indicating additional non-KATP dependent pathways. Extract stimulated cellular glucose uptake and insulin action and inhibited starch digestion, protein glycation, DPP-IV enzyme activity and glucose diffusion. Oral HWAS improved glucose tolerance and plasma insulin in high-fat fed obese rats. Treatment for 9 days with HWAS (250 mg/5 mL/kg), partially normalised energy intake, body weight, pancreatic insulin content, and both islet size and beta cell mass. This was associated with improved oral glucose tolerance, increased plasma insulin and inhibition of plasma DPP-IV activity. Isolated insulinotropic compounds, including rutin (C27H30O16), recapitulated the positive actions of HWAS on beta cells and in vivo glucose tolerance and plasma insulin responses. Annona squamosa is attractive as a dietary adjunct in treatment of T2DM and as a source of potential antidiabetic agents including rutin.

中文翻译:


鳞状苋菜抗糖尿病和胰岛素释放作用的评价,包括活性植物化学物质的分离和表征



番荔枝通常被称为“番荔枝”。研究了番荔枝叶热水提取物 (HWAS) 的抗糖尿病作用以及活性促胰岛素化合物的分离。使用BRIN-BD11细胞和分离的小鼠胰岛测定胰岛素释放、膜电位和细胞内Ca 2+ 。 3T3L1 脂肪细胞和体外模型用于测定细胞葡萄糖摄取、胰岛素作用、淀粉消化、葡萄糖扩散、DPP-IV 活性和糖化。使用葡萄糖不耐症高脂肪喂养的大鼠进行体内研究。通过 HPLC、LCMS 和 NMR 分离并表征活性化合物。 HWAS 刺激克隆 β 细胞和小鼠胰岛释放胰岛素。使用荧光指示剂染料和胰岛素分泌调节剂,效果可归因于β细胞的去极化和Ca 2+的流入。异丁基甲基黄嘌呤 (IBMX)、甲苯磺丁脲或 30 mM KCl 刺激分泌,表明存在其他非 K ATP依赖性途径。提取物刺激细胞葡萄糖摄取和胰岛素作用,并抑制淀粉消化、蛋白质糖化、DPP-IV 酶活性和葡萄糖扩散。口服 HWAS 改善了高脂喂养的肥胖大鼠的葡萄糖耐量和血浆胰岛素。使用 HWAS (250 mg/5 mL/kg) 治疗 9 天,能量摄入、体重、胰腺胰岛素含量以及胰岛大小和 β 细胞质量部分正常化。这与改善口服葡萄糖耐量、增加血浆胰岛素和抑制血浆 DPP-IV 活性有关。 分离的促胰岛素化合物,包括芦丁 (C 27 H 30 O 16 ),概括了 HWAS 对 β 细胞以及体内葡萄糖耐量和血浆胰岛素反应的积极作用。番荔枝作为治疗 T2DM 的饮食辅助剂以及作为包括芦丁在内的潜在抗糖尿病药物的来源非常有吸引力。
更新日期:2020-10-12
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