Investigation of the Diuretic Potential of Diosmetin, a Flavonoid from Citrus lemon in Sprague-Dawley Rat Model

Diosmetin is a flavonoid present in citrus fruit like lemon. Interestingly, lemon juice has been reported for its diuretic activity. Therefore, experiments were carried out to study the effects of diosmetin as a diuretic agent. The present study aimed to investigate diosmetin's diuretic activity in Sprague Dawley (SD) rats after acute and prolonged administration of different doses. The acute diuretic activity of diosmetin was studied in normal rats at a dose of 20, 40, and 50 mg/kg, p.o., while prolonged diuretic activity was performed by administering the highly significant dose (50 mg/kg) for 7 days. The volume of urine, Na+ and K+ levels, and pH had been estimated with the help of urine samples collected after 6 hrs of normal saline-loaded rats. Also, the involvement of muscarinic receptors, prostaglandins, and nitric oxide in diosmetin-induced diuretic action was investigated. Moreover, a hematological and histopathological examination was carried out to affirm the safety profile. The pH of all urine samples was also observed. In the acute diuretic study, a potent and significant response (p<0.001) was observed at the dose of 50 mg/kg in comparison to 20 and 40 mg/kg. The values of the diuretic index for the test groups (20, 40, and 50 mg/kg) were observed to be 1.11, 1.15, and 1.56, respectively. The value of Lipschitz showed that, at the dose of 50 mg/kg, the diuretic activity of diosmetin was 57% in comparison with furosemide (100%). In prolonged diuretic study, diosmetin (50 mg/kg) caused significant diuresis and natriuresis. The diuretic action of diosmetin was significantly decreased with atropine pretreatment, indicating the involvement of muscarinic receptors, while no significant change was observed in the response of diosmetin with pretreatment of L-NAME and indomethacin, excluding the involvement of endothelium related mediators (NO and PGI2). Moreover, the hematological analysis indicated that diosmetin at 50 mg/kg exhibited mild changes in blood-related parameters. In addition, histopathological examination indicated no significant pathological changes. However, compared to the control, mild inflammation was observed in diosmetin and furosemide-treated rats. We concluded that diosmetin increased the volume of urine and urine electrolytes (Na+ and K+) concentration in a dose-dependent manner in the acute diuretic study, while a significant response was also observed in the prolonged diuretic model. Therefore, diosmetin may be considered a potential diuretic candidate for further studies.