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Erectile dysfunction (ED) is the inability to achieve/maintain an erection. Because of the side effects, interactions, or ineffectiveness of currently used drugs, novel drug discovery studies are ongoing. The roots of Turkish endemic plants Prangos uechtritzii and Prangos heyniae are traditionally used as aphrodisiacs in Anatolia and contain coumarin-like relaxant compounds. This study aims to reveal the relaxant effect mechanisms of chloroform root extracts of P. heyniae (Ph-CE) and P. uechtritzii (Pu-CE). Isolated organ bath experiments were performed on Swiss albino mouse corpus cavernosum by DMT strip myograph. Relaxant responses to extract (10 -7 -10 -4  g/ml) were obtained in the presence/absence of NO and H 2 S synthesis inhibitors nitro-l-arginine methyl ester (l-NAME, 100 μM) and aminooxyacetic acid (AOAA, 10 mM) respectively. Sodium nitroprusside (SNP, 10 -9 to 10 -4  M) and Na 2 S (10 -6 to 3 × 10 -3  M)-induced relaxations and CaCl 2 (10 -6 to 10 -4  M), KCl (10 -2.1 to 10 -0.9  M) and phenylephrine (3 × 10 -8 to 3 × 10 -5  M)-induced contractions were taken in the presence/absence of the extracts (10 -4  g/ml). Relaxations induced by Ph-CE but not by Pu-CE were inhibited in the presence of l-NAME and AOAA. Ph-CE increased Na 2 S- and SNP-induced relaxations. Ph-CE and Pu-CE decreased the contractions of KCl, phenylephrine, and CaCl 2 . It was concluded that NO and H 2 S synthesis/downstream mechanisms play roles in relaxations of Ph-CE but not in Pu-CE-induced relaxations. Inhibition of calcium influx appears to be involved in the relaxant effect of Ph-CE and Pu-CE. Since the extracts act directly by relaxing smooth muscle or through H 2 S as well as NO, they may be a potential therapeutic agent in diseases such as ED where the bioavailability of NO is impaired., (© 2022 Wiley-VCH GmbH.)

Ethnopharmacological Relevance: Erectile dysfunction (ED) is the most common form of sexual dysfunction which has been the topic of great interest through the history by all cultures. It is now among the most treated health problems in men of all ages that develop under the influence of lifestyle factors and some diseases. Plants are extensively used to cure sexual dysfunction for centuries. Roots of Prangos sp. have been used to improve sexual performance in Anatolian traditional medicine and are rich of coumarin, furanocoumarin and their derivatives. Scientific research is necessary to support and validate the ethno-traditional uses of these plants., Aim of the Study: The aim of this study is to investigate the effects of the root extracts of P. pabularia, P. uechtritzii and P. heyniae on erectile function and to isolate and identify the chemical compounds of the most active extract and reveal possible pharmacological mechanism of the major compound of the extract with the strongest relaxant effect in mouse corpus cavernosum (MCC)., Materials and Methods: The roots of plants were extracted with chloroform, n-hexane and methanol. The compounds were isolated from the extract by column chromatography and structures were identified by NMR and MS. The relaxant effects of extracts (10 -7 -10 -4  g/mL), (+)-oxypeucedanin (10 -7 -10 -4  M) and Na 2 S (10 -7 -3 × 10 -3  M) were tested in MCC strips by DMT myograph. To investigate the mechanism, the synthesis inhibitors of aminooxyacetic acid (AOAA, 10 -2  M) and nitro-L-arginine methyl ester (L-NAME, 10 -4  M) were used, respectively. H 2 S formation was evaluated basal and L-cysteine (L-cyst)-stimulated conditions by H 2 S microsensor., Results: All extracts relaxed MCC in a concentration dependent manner. The maximum relaxing effects were achieved with chloroform extracts. Chloroform extract of P. pabularia (Pp-CE) was more potent than the others. Pp-CE-induced relaxations were significantly decreased by AOAA and L-NAME. (+)-Oxypeucedanin, the major compound of Pp-CE, induced relaxant responses and this effect was inhibited by AOAA, but not L-NAME. The relaxation of (+)-oxypeucedanin was found to be similar in view of E max to positive control H 2 S donor Na 2 S. (+)-Oxypeucedanin increased L-cyst-stimulated H 2 S formation. Augmentation of H 2 S synthesis with (+)-oxypeucedanin was inhibited by AOAA., Conclusions: Pp-CE has the strongest effect on relaxation of MCC and this result supports the traditional aphrodisiac use of P. pabularia root extract in Anatolia. The pharmacological mechanisms of Pp-CE to relax MCC involve NO and H 2 S formation. (+)-Oxypeucedanin could be responsible for the H 2 S-mediated relaxations of Pp-CE in MCC., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Erectile dysfunction (ED) is defined in relation to the metabolic syndrome (metS). Hydrogen sulphide (H 2 S), a gasotransmitter, has been revealed to get involved in hypertension, insulin secretion and regulation of vascular tone especially in erectile physiology. This study aimed to investigate the effect of H 2 S on metS-induced ED. Animals were divided into two groups as control and metS, which were fed with standard diet or 60% high-fructose diet for 10 weeks respectively. The metS model was evaluated with biochemical analyses, waist circumference/tibia length ratio and HOMA index. Penile hemodynamic parameters were evaluated by the measurement of intracavernous pressure/mean arterial pressure ratio during cavernous nerve stimulation in the presence and absence of intracavernous injection of NaHS (100 μg/50 μl) and its control 0.9%NaCl (50 μl) in both groups. H 2 S levels were measured in penile tissues by methylene blue assay. H 2 S levels were significantly decreased in the penile tissues of the metS group. Decreased intracavernous pressure/mean arterial pressure ratio improved after intracavernous administration of NaHS in the metS group. These results suggest the significant role of H 2 S in the metS-induced erectile dysfunction that could be a new therapeutic target., (© 2017 Blackwell Verlag GmbH.)

Erectile dysfunction (ED) is considered as a marker for cardiovascular diseases. Nitric oxide (NO) deficiency is the major cause of erectile dysfunction (ED). The role of hydrogen sulfide (H 2 S) in erection has recently been recognized and is receiving attention as a pharmacological target. Several studies have focused on the effect of H 2 S on NO-dependent relaxation, but the role of NO on H 2 S in penile tissue has not been studied yet. Unlike NO, H 2 S is mainly synthesized from smooth muscle cells rather than endothelial cells. We hypothesized that H 2 S may compensate for the decreased NO bioavailability and may be beneficial in severe ED where endothelial dysfunction is present. Thus we studied the effect of NO deficiency on H 2 S formation and vasorelaxation induced by l-cysteine, which is the substrate of the H 2 S producing enzymes in mice corpus cavernosum (MCC). NO deficiency induced by Nω-Nitro-l-arginine (L-NNA) was confirmed by the inhibition of acetylcholine-induced relaxation. l-cysteine, the substrate for the endogenous H 2 S production, caused a concentration-dependent relaxation that was reduced by CBS/CSE inhibitor aminooxyacetic acid (AOAA) in MCC strips. L-NNA caused a significant increase in l-cysteine-induced relaxation, and this effect was reversed by AOAA. On the contrary, no change in relaxation to NaHS (exogenous H 2 S donor) in MCC was observed. L-NNA increased H 2 S formation stimulated by l-cysteine in wild type MCC but not in CSE -/- mice. In parallel, the expression of both cysthationine γ lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST) was increased, whereas cysthationine-β synthase (CBS) was decreased in eNOS -/- MCC. We conclude that H 2 S plays a compensatory role in the absence of NO by enhancing the relaxation induced by endogenous H 2 S through CSE and 3-MPST in MCC, without altering downstream mechanisms. We suggest that H 2 S-targeting drugs may provide the maintenance of compensatory treatment in ED patients. This may be more relevant in ED with severe endothelial dysfunction, as H 2 S is mainly derived from smooth muscle., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Resveratrol (RVT) found in red wine protects against erectile dysfunction and relaxes penile tissue (corpus cavernosum) via a nitric oxide (NO) independent pathway. However, the mechanism remains to be elucidated. Hydrogen sulfide (H2 S) is a potent vasodilator and neuromodulator generated in corpus cavernosum., Aims: We investigated whether RVT caused the relaxation of mice corpus cavernosum (MCC) through H2 S., Methods: H2 S formation is measured by methylene blue assay and vascular reactivity experiments have been performed by DMT strip myograph in CD1 MCC strips., Main Outcome Measures: Endothelial NO synthase (eNOS) inhibitor Nω-Nitro-L-arginine (L-NNA, 0.1 mM) or H2 S inhibitor aminooxyacetic acid (AOAA, 2 mM) which inhibits both cystathionine-β-synthase (CBS) and cystathionine-gamma-lyase (CSE) enzyme or combination of AOAA with PAG (CSE inhibitor) has been used in the presence/absence of RVT (0.1 mM, 30 min) to elucidate the role of NO or H2 S pathways on the effects of RVT in MCC. Concentration-dependent relaxations to RVT, L-cysteine, sodium hydrogen sulfide (NaHS) and acetylcholine (ACh) were studied., Results: Exposure of murine corpus cavernosum to RVT increased both basal and L-cysteine-stimulated H2 S formation. Both of these effects were reversed by AOAA but not by L-NNA. RVT caused concentration-dependent relaxation of MCC and that RVT-induced relaxation was significantly inhibited by AOAA or AOAA + PAG but not by L-NNA. L-cysteine caused concentration-dependent relaxations, which are inhibited by AOAA or AOAA + PAG significantly. Incubation of MCC with RVT significantly increased L-cysteine-induced relaxation, and this effect was inhibited by AOAA + PAG. However, RVT did not alter the effect of exogenous H2 S (NaHS) or ACh-induced relaxations., Conclusions: These results demonstrate that RVT-induced relaxation is at least partly dependent on H2 S formation and acts independent of eNOS pathway. In phosphodiesterase 5 inhibitor (PDE-5i) nonresponder population, combination therapy with RVT may reverse erectile dysfunction via stimulating endogenous H2 S formation., (© 2015 International Society for Sexual Medicine.)