Abstract
In order to increase the oral bioavailability and antidiabetic effect of amentoflavone with multimechanisms, an oral micelle system was developed by using a N-vinyl pyrrolidone-maleate-guerbet alcohol monoester polymer for the first time, which was designated as P(NVP-MGAM)/AF. After oral administration, P(NVP-MGAM)/AF enhanced the oral bioavailability of amentoflavone, which was approximately 3.2 times that of amentoflavone solution. The animal study using the KKAy insulin-resistant diabetes mouse model indicated that it regulates the expression and activity of downstream signaling factors and proteins by lowering blood lipids, reducing inflammatory responses and activating the peroxisome proliferator-activated receptor (PPAR) γ signaling pathway and PI3K/Akt signaling pathway. After being made into micelles, it is more effective because of its better absorbability and bioavailability. The results from this study provide a theoretical basis for the clinical application of amentoflavone for diabetes treatment. The oral micelles of P(NVP-MGAM)/AF may become one of the most potent drugs in the treatment of diabetes mellitus, which opens up a new way for the prevention and treatment of diabetes.
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