Abstract:
Phenolics of mulberry (Morus alba L.) leaves (MLs) have potential anti-diabetic effects, but they may be chemically modified during gastrointestinal digestion so affect their biological activity. In this study, an in vitro digestion model coupled with Caco-2 monolayer and Caco-2/insulin-resistant HepG2 coculture model were used to study the transport and hypoglycemic effects of phenolics in raw MLs (U-MLs) and solid-fermented MLs (F-MLs). The results of LC-MS/MS analysis showed that the Papp (apparent permeability coefficient, 10-6cm/s) of phenolics in digested MLs ranged from 0.002 ± 0.00 (quercetin 3-O-glucoside) to 60.19 ± 0.67 (ferulic acid), indicating higher phenolic acids absorbability and poor flavonoids absorbability. The Papp values of phenolic extracts of F-MLs in Caco-2 monolayer were significantly higher (p > 0.05) than that of U-MLs. Digested phenolic extracts inhibited the activities of sucrase (60.13 ± 2.03 %) and maltase (82.35 ± 0.78 %) and decreased 9.28 ± 0.84 % of glucose uptake in Caco-2 monolayer. Furthermore, a decrease in the mRNA expression of glucose transporters SGLT1 (0.64 ± 0.18), GLUT2 (0.14 ± 0.02) and the sucrase-isomaltase (0.59 ± 0.00) was observed. In Caco-2/insulin-resistant HepG2 co-culture model, phenolic extracts regulated glucose metabolism by up-regulating the mRNA expressions of IRS1 (9.32-fold), Akt (17.07-fold) and GYS2 (1.5-fold), and down-regulating the GSK-3β (0.22-fold), PEPCK (0.49-fold) and FOXO1 (0.10-fold) mRNA levels. Both U-MLs and F-MLs could improve glucose metabolism, and the partial least squares (PLS) analysis showed that luteoforol and p-coumaric acid were the primary phenolics that strongly correlated with the hypoglycemic ability of MLs. Results suggested that phenolics of MLs can be used as dietary supplements to regulate glucose metabolism.
摘要:
桑树(桑树)叶(MLs)的酚类物质具有潜在的抗糖尿病作用,但它们可能在胃肠道消化过程中被化学修饰,因此会影响其生物活性。在这项研究中,采用体外消化模型与Caco-2单层和Caco-2/胰岛素抵抗HepG2共培养模型相结合,研究了酚类物质在原始MLs(U-MLs)和固体发酵MLs(F-MLs)中的转运和降血糖作用.LC-MS/MS分析结果表明,Papp(表观渗透系数,10-6cm/s)消化的MLs中的酚类物质范围从0.002±0.00(槲皮素3-O-葡萄糖苷)到60.19±0.67(阿魏酸),表明较高的酚酸吸收性和较差的类黄酮吸收性。Caco-2单层中F-MLs的酚类提取物的Papp值显著高于U-MLs(p>0.05)。消化的酚类提取物抑制了蔗糖酶(60.13±2.03%)和麦芽糖酶(82.35±0.78%)的活性,并降低了Caco-2单层中9.28±0.84%的葡萄糖摄取。此外,葡萄糖转运蛋白SGLT1的mRNA表达下降(0.64±0.18),观察到GLUT2(0.14±0.02)和蔗糖酶-异麦芽糖酶(0.59±0.00)。在Caco-2/胰岛素抵抗HepG2共培养模型中,酚类提取物通过上调IRS1的mRNA表达(9.32倍)来调节葡萄糖代谢,Akt(17.07倍)和GYS2(1.5倍),并下调GSK-3β(0.22倍),PEPCK(0.49倍)和FOXO1(0.10倍)mRNA水平。U-MLs和F-MLs都可以改善葡萄糖代谢,偏最小二乘法(PLS)分析显示,与MLs的降血糖能力密切相关的主要酚类物质为芦荟酚和对香豆酸。结果表明,MLs的酚类物质可以作为膳食补充剂来调节糖代谢。