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【Neohesperidin】Main Citrus Flavonoids with Antidiabetic Effects

【Neohesperidin】Main Citrus Flavonoids with Antidiabetic Effects

Neohesperidin (hesperetin-7-neohesperidoside) is a flavanone glycoside, a weak-polar molecule with a bitter taste, found in various citrus fruits. Neohesperidin, a dihydrochalcone, is a substance mainly obtained from bitter oranges and has unique properties such as masking undesirable flavors and enhancing fruity and citrus flavors, which gives this molecule great value for the food industry and nutraceuticals firms. This flavanone has a wide range of biological activities, including neuroprotective activity and anti-proliferative effects. Recently, Neohesperidin was found to inhibit common allergic responses in vivo and in vitro, exhibit protective effects in progressive pulmonary fibrosis, and show anti-osteoclastic properties, presenting it as a potential anti-catabolic biomolecule for the treatment of osteoporosis.

The antidiabetic potential of Neohesperidin was investigated by Jia et al., who evaluated the effect of this active compound derived from Citrus aurantium Linn. in diabetic KK-Ay mice induced via a formulated diet (6.0% fat, 18% proteins, and 8.0% water). Neohesperidin had no significant effect on the body weight and food intake in the experimental diabetic mice; nevertheless, it increased glucose tolerance and insulin sensitivity and reduced the blood glucose levels affected by diabetic illness. Neohesperidin treatment also significantly reduced total cholesterol and TG, in addition to decreasing ALT, but it did not modulate AST levels, showing its key hypoglycemic and hypolipidemic properties.

Histological studies showed that Neohesperidin-treated diabetic mice had a marked reduction in lipid accumulation in the liver and decreased adipocyte size compared with water-treated KK-Ay diabetic mice. Neohesperidin was shown to have hypolipidemic effects via exerting a profound influence on markers, such as the mRNA levels of PPAR-α, PPAR-γ, and their target genes, including stearoyl-CoA desaturase (SCD)-1, carnitine palmitoyltransferase (CPT)-1, adaptor complex (AP)-2, UCP-2, fatty acid synthase (FAS), and acyl-CoA oxidase (ACOX), in liver tissue. The expression of SCD-1 and FAS in diabetic mice was significantly down-regulated by Neohesperidin treatment, whereas the expression of ACOX was significantly up-regulated. Finally, Neohesperidin treatment resulted in the increased phosphorylation of AMPK. These data demonstrate that Neohesperidin may have pronounced potential for the prevention of obesity-linked diabetes mellitus.

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