Although therapeutic effect of quercetin (Quer) was reported on non-alcoholic fatty liver disease (NAFLD), destructive effects have been shown on male fertility due to its pro-oxidative properties. On the other hand, NAFLD impairs germ cells to produce sperm and leads to male infertility. Herein, a biocompatible and green bigel was designed for Quer delivery to prevent infertility induced by NAFLD as the increasing complications. Bigels were prepared using cottonseed oil/cannabis oil/alginate/ferula gum and optimized by the mixture design method. NAFLD was induced by 58% of dietary calorie as lard and 42 g/L fructose for 16 weeks in Sprague-Dawley rats. So on animals received 2 mg/kg Quer loaded on bigels, free bigels, or free Quer for 45 days as daily gavage. Semen was analyzed, followed by the assessment of DNA integrity. Count, motility, and normal morphology reached the healthy control group at the bigel-Quer-treated one. Moreover, all of these parameters were significantly higher in the bigel-Quer group than the Quer and bigel, alone. The percent of sperms with head and tail abnormality decreased considerably in the bigel-Quer group compared with the Quer, free bigel, and NAFLD groups. Serum testosterone levels significantly increased and reached the healthy control group in the bigel-Quer group. DNA fragmentation of sperm significantly decreased in the bigel-Quer group (p < 0.05). The bigel showed synergistic effects with Quer for treating infertility in rats with NAFLD.

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