The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice

Abstract

Polyphenols are representative bioactive substances with diverse biological effects. Here, we show that apigenin, a flavonoid, has suppressive effects on microRNA (miRNA) function. The effects were mediated by impaired maturation of a subset of miRNAs, probably through inhibition of the phosphorylation of TRBP, a component of miRNA-generating complexes via impaired mitogen-activated protein kinase (MAPK) Erk activation. While glucose intolerance was observed in miRNA103 (miR103)-overexpressing transgenic mice, administration of apigenin improved this pathogenic status likely through suppression of matured miR103 expression levels. These results suggest that apigenin may have favorable effects on the pathogenic status induced by overexpression of miRNA103, whose maturation is mediated by phosphorylated TRBP.

Persimmon tannin alleviates hepatic steatosis in L02 cells by targeting miR-122 and miR-33b and its effects closely associated with the A type ECG dimer and EGCG dimer structural units

“…It was reported that TRBP phosphorylation enhanced the maturation of miRNAs through stabilization of the miRNA-generating complex (Paroo et al, 2009). Administration of apigenin suppressed expression of miR-103 in miR-103 transgenic mice by inhibiting TRBP phosphorylation (Ohno et al, 2013). On the other hand, polyphenols may bind to miRNAs directly.…”

Citrus medicaL. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

“…The administration of this flavonoid at the dose of 4 mg/kg bw/day after 1 week determined the reduction of blood GLU levels and demonstrated an efficient protection on liver and kidney. Moreover, apigenin improved GLU tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice 25 . Escande et al 26 described the ability of apigenin and quercetin to increase intracellular nicotinamide adenine dinucleotide (NAD + ) levels by the inhibition of enzyme CD38.…”

“…A mixture of 1.5 ml of 0.25 mm DPPH solution in ethanol and 12 ml of CD extract at different concentrations was prepared and allowed to reach a steady state at 25 C for 30 min. The bleaching of DPPH was measured at 517 nm with UV-vis Jenway 6003 spectrophotometer (Milan, Italy).…”

Apigenin Causes Biochemical Modulation, Glut4 and Cd38 Alterations to Improve Diabetes and to Protect Damages of Some Vital Organs in Experimental Diabetes

“…This compound has been reported to have anti-inflammatory, antioxidant and anti-carcinogenic properties . Apigenin has been reported to improve glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice (Ohno et al, 2013). Detailed investigation related to antidiabetic potential of apigenin still remains elusive.…”

“…Apigenin was dissolved in water containing 0.1% v/v Dimethyl Sulfoxide (DMSO) for animal treatment according to the earlier report (Ohno et al, 2013). Absorption and elimination phase of apigenin via oral route is very slow and biological t 1/2 of apigenin is 91.8 h. As metabolism is slow, apigenin has general tendency to accumulate in tissue after oral administration.…”