Supramolecular aggregates of myricetin improve its bioavailability and its role in counteracting alcoholism

Acute alcoholism often induces lesions in multiple organs. There is currently no specific treatment for acute alcoholism in clinical practice. Few people know the anti-alcoholic effect of myricetin (MYR). It is known to have some potential to combat alcoholism based on our preliminary experiments. Additionally, its poor water solubility limits its efficacy. The purpose of this study is to enhance the anti-alcoholic effect by improving the solubility using Kolliphor ® HS15 to prepare supramolecular aggregates of MYR (MYR-SA). The solubility of MYR-SA in water was increased more than 1785-fold. Due to p-gp inhibition by HS15, the Ka and Peff of MYR-SA were about 10-fold higher than pure MYR, respectively, assayed in the intestinal perfusion model. Pharmacokinetic revealed that the AUC0-t of MYR-SA was 2.17-fold higher than that of MYR. Upon administration of MYR-SA in intoxicated animals, the highest blood alcohol level was significantly decreased by 44.9%, the onset of LORR (Loss of righting reflex) was prominently prolonged 3.13-fold. In addition, MYR-SA significantly increased the enzymatic activities of ADH and ALDH in mice (p < 0.01). MYR-SA dramatically reduced oxidative stress and protected mouse gastric mucosa from ethanol-stimulated injury. In summary, MYR-SA showed excellent performance in counteracting alcoholism by improving the oral bioavailability of MYR greatly.