Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Plan de San Luis y Salvador Díaz Mirón S/N, Col. Casco de Santo Tomás, CP 11340 CDMX, Mexico.
UMAE Hospital de Especialidades 2° Piso CORSE Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, CP 06720 CDMX, Mexico.
Molecules. 2020 Jul 24;25(15):3361. doi: 10.3390/molecules25153361.
Safford and two acyclic terpenoids were evaluated to determine their antihyperglycemic activity as potential α-glucosidase and selective SGLT-1 inhibitiors. Ethanolic extract (EEAd), chloroformic (CHClFr), ethyl acetate (EtOAcFr), aqueous residual (AcRFr), secondary 5 (Fr5) fractions, farnesal (), and farnesol () were evaluated on normoglycemic and streptozocin-induced diabetic mice. EEAd, CHClFr, Fr5, () and () showed antihyperglycemic activity. The potential as α-glucosidase inhibitors of products was evaluated with oral sucrose and lactose tolerance (OSTT and OLTT, respectively) and intestinal sucrose hydrolysis (ISH) tests; the potential as SGLT-1 inhibitors was evaluated using oral glucose tolerance (OGTT), intestinal glucose absorption (IGA), and urinary glucose excretion (UGE) tests. In OSTT and OLTT, all treatments showed significant activity at two and four hours. In ISH, half maximal effective concentrations (CE) of 565, 662 and 590 μg/mL, 682 and 802 μM were calculated, respectively. In OGTT, all treatments showed significant activity at two hours. In IGA, CE values of 1059, 783 and 539 μg/mL, 1211 and 327 μM were calculated, respectively. In UGE Fr5, () and () showed significant reduction of the glucose excreted compared with canagliflozin. These results suggest that the antihyperglycemic activity is mediated by α-glucosidase and selective SGLT-1 inhibition.
萨福德和两种无环萜烯被评估为潜在的α-葡萄糖苷酶和选择性 SGLT-1 抑制剂，以确定其降血糖活性。乙醇提取物 (EEAd)、氯仿部分 (CHClFr)、乙酸乙酯部分 (EtOAcFr)、水残留部分 (AcRFr)、二级 5 部分 (Fr5)、法呢醛 () 和法呢醇 () 在正常血糖和链脲佐菌素诱导的糖尿病小鼠中进行了评估。EEAd、CHClFr、Fr5、() 和 () 表现出降血糖活性。通过口服蔗糖和乳糖耐量 (OSTT 和 OLTT) 和肠蔗糖水解 (ISH) 试验评估产物作为α-葡萄糖苷酶抑制剂的潜力；通过口服葡萄糖耐量 (OGTT)、肠葡萄糖吸收 (IGA) 和尿葡萄糖排泄 (UGE) 试验评估作为 SGLT-1 抑制剂的潜力。在 OSTT 和 OLTT 中，所有治疗均在两小时和四小时时表现出显著的活性。在 ISH 中，计算出 565、662 和 590μg/mL、682 和 802μM 的半最大有效浓度 (CE)。在 OGTT 中，所有治疗均在两小时时表现出显著的活性。在 IGA 中，计算出 1059、783 和 539μg/mL、1211 和 327μM 的 CE 值。在 UGE 中，Fr5、() 和 () 与坎格列净相比，显示出葡萄糖排泄量的显著减少。这些结果表明，降血糖活性是通过α-葡萄糖苷酶和选择性 SGLT-1 抑制介导的。
