In vitro and in vivo investigation of natural compounds from seed extract of Mucuna pruriens lacking L-DOPA for treatment of erectile dysfunction

Objective:To investigate the biological effects of the Mucuna pruriens(M.pruriens)seed extracts that lacked of L-DOPA,which was formerly reported as the active ingredient,on erectile dysfunction(ED)both in vitro and in vivo.Methods:Seed of M.pruriens plant that cultivated in Mae Taeng District,Chiang Mai Province,Thailand,was collected.Component of its seeds were extracted and isolated into 2 fractions using methanol,polar and nonpolar.Each fraction was investigated for phytochemicals using GC/MS and was screened for biological activity In vitro using three different cell lines.The most biological active fraction was used to treat to both steptozotocin(STZ)-induced diabetes mellitus-erectile dysfunction(DM-ED)male wistar rats and normal rats(n=6 per groups)to compare the effect on sexual behaviour parameters,including number of intromission,mounting and ejaculation,with that of rats given Sildenafil by individually pairing with their female counterparts.Penile tissues and serums were collected to determine histological structure,related gene expression and biomolecules.Results:The phytochemicals of the polar fraction were possibly catechol and its derivatives plus polyphenols,whereas the nonpolar fraction consisted of lipid derivatives.L-DOPA was not detected in either of the extracts.The polar fraction was able to up-regulate the expression of ED-related genes including e NOS and n NOS in vitro which subsequently promotes NO production and maintains intracellular cG MP levels.When administrated to DM-ED rats,the polar extract significantly improved all sexual behaviour parameters in DM-ED rats compare to untreated group(18.3±1.8 to 10.8±2.9 for intromission,9.8±2.2 to 5.7±1.3 for mounting,and 1.8±0.6 to 0.2±0.4 for ejaculation).That effect might due to the ability of the extract to stimulate the expression of eN OS and nN OS which results in NO production and subsequently maintains cG MP levels in penile tissue.Moreover,this extract may also prevent penile tissue deterioration due to diabetes.Conclusions:The polar extract of M.pruriens seed can be used for ED therapy,especially in patients with metabolic diseases including diabetes.The action of the extract might be due to catechol and its derivatives and polyphenols.