Aims: This study aimed to investigate the effects of consuming Phoenix dactylifera and fasting on the mRNA expression of major hepatic drug-metabolizing enzymes in mice. Methods: Phoenix dactylifera ethanolic extract was analyzed using LC-MS/MS. We used forty-two male Balb/c mice which were treated with low (300 mg/kg) and high (2583 mg/kg) doses of Phoenix dactylifera and fasted for 24 hours, two weeks, and one month. Then, we analyzed the expression of cyp3a11, cyp2c29, cyp2d9, and ugt2b1 using real-time polymerase chain reaction assay. In addition, we assessed the relative liver weights of the mice and the hepatic phathohistological alterations. Results: We found that Phoenix dactylifera ethanolic extract contained 38 phytochemical compounds mainly kaempherol, campesterol, lutein, apigenin, genistein, and isoquercetin. Fasting significantly upregulated the mRNA expression of several drug-metabolizing enzymes in a time-dependent manner and we showed that consuming the low dose of Phoenix dactylifera significantly upregulated the expression of drug-metabolizing enzymes more than the high dose. The results of the histological examinations and relative liver weight showed that fasting and consuming of Phoenix dactylifera did not cause any toxicological alterations in the liver of the mice. Conclusion: It is concluded from this study that fasting and consuming of Phoenix dactylifera upregulated the mRNA expression of major drug-metabolizing enzymes in mouse livers. These findings may explain, at least partly, the variation of drug response during fasting of the month of Ramadan and would direct future clinical studies in optimizing dosing of pharmacotherapeutic regimen.

Background: Anxiety is one of the most frequent psychiatric disorders, affecting 33.7% of the general population. However, the consumption of healthy diets has been found to help, at least in part, in the prevention and treatment of anxiety-like disorders. Methods: In this study, the anxiety behaviors of mice subjected to chronic intake of low-and high doses of ethanolic extract of Medjool dates (Phoenix Dactylifera) were evaluated in comparison to the counterparts of control mice. The elevated zero maze (EZM) test and marbles burying test were used as models of choice for evaluating anxiety behaviors in these mice. In addition, aphytochemical analysis of major secondary metabolite groups was done. Results: The findings of this study revealed that the ethanolic extract of dates is rich in flavonoids and steroids with known activity as anxiolytics, such as kaempherol. Mice received a low dose (300 mg/kg) of the extract exhibited lower anxiety in the EZM than the untreated mice (negative control), which was determined by a significant increase in the latency to the closed area, a significant decrease in the time spent in the closed area and a significant increase in the number of the entries to the open quadrants. The anxiolytic effect of low dose extract was comparable to that produced in positive control mice treated with diazepam (1.5 mg/kg, i.p) in all tested parameters. Data obtained from the marble burying test also showed a significant anxiolytic effect by low dose (300 mg/kg) of the extract as compared to untreated mice, which was manifested by significant decrease in the total number of buried marbles. The anxiolytic effect of low dose extract in the marbles burying test was comparable to that produced in counterparts of positive control mice treated with fluoxetine (5mg/kg, i.p). On the other hand, chronic intake of high doses (2583 mg/kg) of the extract did not cause any significant anxiolytic effect in the EZM and marbles burying tests. Conclusions: Overall, these results indicate that regular intake of low dose of ethanolic extract of Medjool dates may help to prevent and manage anxiety disorders. However, further studies are recommended to elucidate the putative mechanism underlying the anxiolytic effect of these dates.