Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes-Induced Sexual Dysfunction of Rats

Abstract

IntroductionDiabetes-induced sexual dysfunction is associated with an increase in oxidative stress. Scavengers of reactive oxygen species (ROS) have been shown to reduce oxidative stress and aid in the management of sexual dysfunction in diabetes.AimThe aim of the study was to test the hypothesis that antioxidant, which scavenge ROS and reduce formation of advanced glycation end products (AGEs), can potentiate efficacy of phosphodiesterase type 5 inhibitors in diabetes-induced sexual dysfunction that is associated with oxidative stress.Materials and MethodsEffect of phloroglucinol and sildenafil on serum glucose level, sexual function, penile smooth muscle : collagen ratio, and phenylephrine precontracted corpus cavernosum smooth muscle (CCSM) was studied. The ability of phloroglucinol to reduce the formation of AGEs and its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) was also evaluated.Main Outcome MeasuresAntioxidant potential of phloroglucinol was studied in addition to its effect on diabetes-induced sexual dysfunction in presence and absence of sildenafil.ResultsPhloroglucinol (50 mg/kg, p.o.) significantly decreased serum glucose level and increased sexual function in streptozotocin-induced diabetic rats when compared with diabetic control rats. Sildenafil (5 mg/kg, p.o.) had no effect on glycemia but significantly increased sexual function of diabetic rats. Coadministration of phloroglucinol increased the efficacy of sildenafil by improving sexual function. Treatment of diabetic rats with phloroglucinol + sildenafil maintained smooth muscle : collagen levels similar to that of normal rat penile tissue. Phloroglucinol decreased formation of AGEs and significantly scavenged DPPH radical activity in vitro. Sildenafil relaxed isolated CCSM of normal rat and diabetic rat significantly, but phloroglucinol did not show any significant effect. Phloroglucinol also inhibited human CYP3A4 enzyme activity in vitro.ConclusionPhloroglucinol coadministration increases efficacy of sildenafil in diabetes-induced sexual dysfunction. However, further studies are required to ascertain the benefits of phloroglucinol owing to its undesirable CYP3A4 inhibition activity.

Protective effects of <i>Lycium barbarum</i> polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice

“…Reports indicated Sildenafil, as a first-line medicine for treatment of erectile dysfunction and sexual dysfunction, increased sperm quantity and quality [29,51]. Our experiment showed similar findings, but the LBP showed a better reversal effect on the fertility impairment than sildenafil which might be caused by more mechanisms of action.…”

Allantoin Alleviates Male Sexual Dysfunction in Diabetic Rats through Augmenting the Level of Testosterone

“…Coordinated relaxation of penile smooth and penile arteries results in persistent penile erection required for sexual activity. 6,12,13,15,18 Interestingly, testosterone, a male sex hormone stimulates and maintains the NOS. [29][30][31] We estimated nitrite, the stable metabolite of NO in the serum of rats.…”

“…21,22,23 In animal model also diabetes decreases sexual function. 6,18 Namely, sexual desire was decreased as evident from the increase in ML and IL. Erectile function was also decreased as evident from the decrease in IF and increase in PEI.…”

“…Erectile function was also decreased as evident from the decrease in IF and increase in PEI. 6,13,18 Treatment of allantoin increased the sexual function in diabetic rats. This could be due to an increase in endothelial function which was evident from the decrease in hypertension.…”

“…Natural products with antioxidant potential have been proven to improve sexual function and ameliorate diabetes-induced sexual dysfunction. 4,5,6 Allantoin (ALL) is the active constituent found in yam (sweet potato), plant from Dioscorea species. 7 Allantoin is widely used in the prevention of inflammation and ulcers.…”