Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
J Agric Food Chem. 2020 Apr 1;68(13):3976-3985. doi: 10.1021/acs.jafc.0c00515. Epub 2020 Mar 23.
Isorhapontigenin is a natural bioactive stilbene isolated from various plants and fruits. It has been reported to exhibit several physiological activities including anticancer and anti-inflammation activity in vitro and in experimental animal models. This study aimed to investigate whether isorhapontigenin exerts antidiabetic effects in vivo. To this end, diabetic mice were treated with either 25 mg kg of isorhapontigenin or vehicle intraperitoneally for a period of 5 weeks. The results show that isorhapontigenin treatment significantly reduced postprandial levels of glucose, insulin, as well as free fatty acid, three markers of diabetes. Further studies show that isorhapontigenin treatment markedly improves insulin sensitivity and glucose tolerance of mice as shown by ITT and GTT. Together, these physiological results show that isorhapontigenin possesses antidiabetic properties in vivo. Mechanistically, the isorhapontigenin-mediated antidiabetic effect is caused by favorable changes in adipose tissue, including reductions in adipocyte diameter and improved adipose insulin sensitivity. Further studies with 3T3-L1 cells show that isorhapontigenin treatment promotes preadipocyte differentiation by upregulation of the activity of the master adipogenic regulator PPARγ and deceleration of its proteasomal degradation. Together, our results establish for the first time an important role of isorhapontigenin as a potential nutraceutical agent for diabetes treatment.
异落叶松脂素是一种从多种植物和水果中分离出来的天然生物活性二苯乙烯。已有研究报道其具有多种生理活性，包括体外和实验动物模型中的抗癌和抗炎活性。本研究旨在探讨异落叶松脂素在体内是否具有抗糖尿病作用。为此，将糖尿病小鼠用 25mg/kg 的异落叶松脂素或载体经腹腔注射治疗 5 周。结果表明，异落叶松脂素治疗可显著降低糖尿病小鼠餐后血糖、胰岛素和游离脂肪酸水平，这三个指标是糖尿病的标志物。进一步的研究表明，异落叶松脂素治疗可显著改善糖尿病小鼠的胰岛素敏感性和葡萄糖耐量，表现为 ITT 和 GTT 试验。综上所述，这些生理结果表明异落叶松脂素在体内具有抗糖尿病作用。从机制上讲，异落叶松脂素介导的抗糖尿病作用是由于脂肪组织的有利变化引起的，包括脂肪细胞直径的减小和脂肪组织胰岛素敏感性的提高。进一步用 3T3-L1 细胞进行的研究表明，异落叶松脂素通过上调主脂肪生成调节剂 PPARγ 的活性和减缓其蛋白酶体降解来促进前脂肪细胞分化。综上所述，我们的研究结果首次确立了异落叶松脂素作为一种潜在的糖尿病治疗营养保健品的重要作用。
