curcumin and Erectile-Dysfunction

Male erectile dysfunction (ED) caused by cavernous nerve injury is a common complication of pelvic surgery, radiotherapy, transurethral surgery or other operations. However, clinical treatment for iatrogenic or traumatic male ED is difficult and not satisfactory. Many studies have shown that curcumin can promote the repair and regeneration of peripheral nerves; however, whether curcumin can rescue cavernous nerve injury is unknown, and the poor bioavailability of curcumin limits its application in vivo. Hence, the study was conducted. A curved slow-release membrane was produced, and the properties were examined. In addition, the effects of the curcumin slow-release membrane on cavernous nerve-injured SD rats were studied. We found that polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) can be used as a good carrier material for curcumin, and curcumin-loaded PLGA-PEG membranes can effectively rescue the cavernous nerve in SD rats, restore the continuity of the cavernous nerve, and increase the expression of nNOS mRNA and proteins in penile tissue, which can improve the penile erectile function of injured SD rats, reduce the degree of penile tissue fibrosis, and effectively promote penis rehabilitation. The curcumin slow-release membrane is proposed to be a new therapeutic approach for penile rehabilitation of cavernous nerve injury.

Topics: Animals; Curcumin; Disease Models, Animal; Erectile Dysfunction; Humans; Male; Penile Erection; Penis; Rats; Rats, Sprague-Dawley; Trauma, Nervous System

Curcumin, a naturally occurring anti-inflammatory compound, has shown promise in pre-clinical studies to treat erectile dysfunction (ED) associated with type-1 diabetes. However, poor bioavailability following oral administration limits its efficacy. The present study evaluated the potential of topical application of curcumin-loaded nanoparticles (curc-np) to treat ED in a rat model of type-2 diabetes (T2D).. Determine if topical application of curc-np treats ED in a T2D rat model and modulates expression of inflammatory markers.. Curc-np (4 mg curcumin) or blank nanoparticles were applied every 2 days for 2 weeks to the shaved abdomen of 20-week-old Zucker diabetic fatty male rats (N = 5 per group). Lean Zucker diabetic fatty male rat controls were treated with blank nanoparticles (N = 5). Penetration of nanoparticles and curcumin release were confirmed by 2-photon fluorescence microscopy and histology. Erectile function was determined by measuring intracorporal pressure (ICP) normalized to systemic blood pressure (ICP/BP) following cavernous nerve stimulation. Corporal tissue was excised and reverse transcription and quantitative polymerase chain reaction used to determine expression of the following markers: nuclear factor (NF)-κβ, NF-κβ-activating protein (Nkap), NF erythroid 2-related factor-2, Kelch-like enoyl-CoA hydratase-associated protein-1, heme oxygenase-1 (HO-1), variable coding sequence-A1, phosphodiesterase-5, endothelial and neuronal nitric oxide synthase, Ras homolog gene family member A, and Rho-associated coiled-coil containing protein kinases-1 and -2.. Erectile function by determination of ICP/BP and expression of molecular markers in corporal tissue by RT-qPCR.. Nanoparticles penetrated the abdominal epidermis and persisted in hair follicles for 24 hours. Curc-np-treated animals exhibited higher average ICP/BP than animals treated with blank nanoparticles at all levels of stimulation and this was statistically significant (P < .05) at 0.75 mA. In corporal tissue, Nkap expression decreased 60% and heme oxygenase-1 expression increased 60% in curc-np- compared to blank nanoparticle-treated animals. ICP/BP values inversely correlated with Nkap and directly correlated with HO-1 expression levels.. These studies demonstrate the potential for topical application of curc-np as a treatment for ED in T2D patients.. The T2D animal model of ED represents a more prevalent disease than the more commonly studied type-1 diabetes model. Although there is improved erectile response in curc-np-treated animals, only at the lower levels of stimulation (0.75 mA) was this significant compared to the blank nanoparticle-treated animals, suggesting more studies are needed to optimize protocols and evaluate toxicity. Topical application of curc-np to a rat model of T2D can systemically deliver curcumin, treat ED, and modulate corporal expression of inflammatory markers. Draganski A, Tar MT, Villegas G, et al. Topically Applied Curcumin-Loaded Nanoparticles Treat Erectile Dysfunction in a Rat Model of Type-2 Diabetes. J Sex Med 2018;15:645-653.

Topics: Administration, Topical; Animals; Curcumin; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Delivery Systems; Endothelium; Erectile Dysfunction; Heme Oxygenase (Decyclizing); Male; Nanoparticles; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Penile Erection; Penis; Protein Precursors; Rats; Rats, Zucker; Salivary Proteins and Peptides

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase-1 (HO-1), Nrf2, NF-B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant increase in NF-Ҡβ, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1, and Nrf2 gene expression, and a significant decrease in NF-Ҡβ, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.

Topics: Animals; Curcumin; Cyclic GMP; Diabetes Mellitus, Experimental; Erectile Dysfunction; Heme Oxygenase-1; Male; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase; p38 Mitogen-Activated Protein Kinases; Penis; Phosphodiesterase 5 Inhibitors; Rats; Tadalafil

Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP).. Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED).. One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes.. Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кβ, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP).. Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кβ, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кβ, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups.. Water-soluble curcumin could enhance erectile function with more effectiveness and with more prolonged duration of action.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Erectile Dysfunction; Heme Oxygenase (Decyclizing); Male; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; p38 Mitogen-Activated Protein Kinases; Penis; Protoporphyrins; Rats