RESUMO
OBJECTIVE: To study of the regulatory effects of the lipid metabolic pathways of trimethylamine-N-oxide (TMAO), flavin-containingmonooxidase 3 (FMO3) and farnesoid X receptor (FXR) on compound stress-induced ED (CSED) rats and the mechanisms of Yimusake Tablets (YMSK) intervention. METHODS: Based on the results of metabonomics analysis, we determined the concentration of TMAO in the serum of the rats in the normal control (n = 30), the CSED model control (n = 30) and the YMSK intervention group (intragastrical administration of YMSK at 250 mg/kg once daily for 2ï¼3 weeks after modeling, n = 30) by nuclear magnetic resonance (NMR) spectroscopy test. We also detected the expressions of the FMO3, FXR1 and FXR2 proteins in the liver tissue of the three groups of rats by Western blot. RESULTS: The serum TMAO level was significantly elevated in the CSED model control compared with that in the normal control group (ï¼»46.64 ± 5.16ï¼½ vs ï¼»34.98 ± 3.69ï¼½ µg/mL, P < 0.01) but remarkably decreased after YMSK intervention (ï¼»39.63 ± 4.81ï¼½ µg/mL) in comparison with that in the CSED model control group (P < 0.01). The rats in the CSED model control group, compared with the normal controls, showed significantly upregulated expressions of FMO3 (1.75 ± 0.90 vs 0.86 ± 0.62, P < 0.01),FXR1 (1.29 ± 0.38 vs 0.78 ± 0.25, P < 0.01) and FXR2 in the liver tissue (1.90 ± 0.63 vs 0.42 ± 0.27, P < 0.01), but all the three expressions were markedly decreased after YMSK intervention (FMO3: 1.05 ± 0.38, P < 0.05; FXR1: 1.07 ± 0.42, P < 0.05; FXR2: 1.04 ± 0.46, P < 0.01) as compared with those in the CSED model control group. CONCLUSIONS: The lipid metabolic pathways of TMAO, FMO3 and FXR underwent significant changes in the rat model of compound stress-induced ED, which could be improved by YMSK intervention, suggesting that YMSK may play an important role in protecting erectile function by regulating the lipid metabolic pathways of TMAO, FMO3 and FXR.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Disfunção Erétil/metabolismo , Metabolismo dos Lipídeos , Metilaminas/sangue , Oxigenases/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Disfunção Erétil/fisiopatologia , Masculino , RatosRESUMO
OBJECTIVE: To evaluate the effects of a combination of Yinyanghuo (Herba Epimedii Brevicornus) (HEB) and Cheqianzi (Semen Plantaginis) (SP) on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats (SHRs), and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor (ACE2/Ang [1-7]/Mas receptor) axis in this process. METHODS: A total of 24 SHRs were randomly assigned to three groups: SHR-control, low-dose (12.5 g/kg) and high-dose (25 g/kg) HEB+SP (HEBSP). Eight Wistar-Kyoto rats were used as normal controls. HEBSP was administered by oral gavage for 28 d. Erectile function was measured once a week using the Heaton test. After 4 weeks of treatment, the corpus cavernosum was harvested from each rat to measure nitric oxide (NO), nitric oxide synthase (eNOS) and Ang (1-7) levels, as well as ACE2, Mas receptor and neuronal nitric oxide synthase (nNOS) protein expression. RESULTS: After 4 weeks of treatment, HEBSP significantly increased erectile function in the treated group compared with SHR-control group (P < 0.01). Additionally, HEBSP treatment significantly increased cavernosal levels of Ang (1-7), eNOS and NO. Moreover, HEBSP significantly elevated the expression levels of ACE2, Mas receptor and nNOS. These beneficial effects were elevated in the high-dose HEBSP group. CONCLUSION: HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang (1-7)/Mas receptor axis, eNOS and nNOS pathways.
Assuntos
Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/metabolismo , Fragmentos de Peptídeos/metabolismo , Angiotensina I/genética , Enzima de Conversão de Angiotensina 2/genética , Animais , Quimioterapia Combinada , Disfunção Erétil/genética , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo I/metabolismo , Ereção Peniana/efeitos dos fármacos , Fragmentos de Peptídeos/genética , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Regulação para Cima/efeitos dos fármacosRESUMO
Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (AT1R) and gp91phox protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of AT1R/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and AT1R/gp91phox expressions and testicular eNOS and StAR expression.
Assuntos
Disfunção Erétil/tratamento farmacológico , Flavonas/uso terapêutico , Hipertensão/tratamento farmacológico , Animais , Aorta Torácica/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/metabolismo , Disfunção Erétil/fisiopatologia , Flavonas/farmacologia , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , NADPH Oxidase 2/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pênis/efeitos dos fármacos , Pênis/metabolismo , Pênis/fisiologia , Fosfoproteínas/metabolismo , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Superóxidos/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. & L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) using various inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K+ channels independently NO signalling pathway.
Assuntos
Óleo de Cravo/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Disfunção Erétil/fisiopatologia , Eugenol/farmacologia , Ereção Peniana/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Disfunção Erétil/etiologia , Disfunção Erétil/metabolismo , Glibureto/farmacologia , Técnicas In Vitro , Injeções , Masculino , Nifedipino/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óleos Voláteis/farmacologia , Pênis/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Guanilil Ciclase Solúvel/antagonistas & inibidores , Tetraetilamônio/farmacologiaRESUMO
Some medicinal mushrooms have effects on sexual dysfunctions. Nitric oxide synthase (NOS)-cyclic gua-nosine monophosphate (cGMP)-phosphodiesterase 5 enzyme (PDE5) pathway is one of the pathophysiological basis of erectile dysfunction (ED). The normal erectile function involves the synthesis of nitric oxide (NO), and the subsequent accumulation of cGMP, whereas cGMP degradation is specifically controlled by PDE5, which promotes corporal smooth muscle cell (SMC) tone and terminates erection. The antioxidant activities of Inonotus obliquus (chaga) water extracts (IO1) and water extraction and alcohol precipitation extracts (IO2) were compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and oxygen radical absorbance capacity (ORAC) method. Three subtypes of NOS (nNOS, iNOS, and eNOS) and PDE5 protein expressions were tested by Western blotting, and cGMP was determined by ELISA on a rat corporal primary SMC. The results revealed that IO2, which had a significantly higher polysaccharide content than IO1, showed a significantly higher ORAC value and a significantly lower half inhibitory concentration for DPPH scavenging activity than IO1. We observed that both IO1 and IO2 increased the expression of eNOS and iNOS significantly compared with the control. Furthermore, when compared with the control, IO1 increased PDE5 expression significantly, while IO2 showed no effect. The different impacts on PDE5 might be the reason that IO2, not IO1, showed significant inducible effect on cGMP compared with the control. This is to our knowledge, the first study exploring the effect of I. obliquus on NOS-cGMP-PDE5 pathway on SMC. The results provide a possible selection of I. obliquus for the treatment of ED.
Assuntos
Agaricales/química , GMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Disfunção Erétil/metabolismo , Inonotus/química , Miócitos de Músculo Liso/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Extratos Vegetais/farmacologia , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/genética , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/genética , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico Sintase/genética , Pênis/metabolismo , Pênis/fisiopatologia , RatosRESUMO
AIMS: Radical prostatectomy (RP) can result in urinary incontinence (UI) and erectile dysfunction (ED), which negatively impact quality of life (QoL). This study aimed to evaluate the effects of a perioperative pelvic floor muscle training (PFMT) program versus usual care on early recovery of urinary continence and erectile function after RP. MATERIALS AND METHODS: Of 59 eligible men, 31 were randomly allocated into 2 groups: Group 1 (Control, N=15) received usual post-RP care; and Group 2 (Physical therapy, N=16) received two pre-RP physical therapist-guided PFMT sessions, including exercises and electromyographic biofeedback, and verbal and written instructions to continue PFMT until RP, which was then resumed after urethral catheter removal. The International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire were used to evaluate UI and ED, respectively. RESULTS: Demographic characteristics were similar in both groups. Three months after RP, the UI rate was 72.7% and 70.0% in Groups 1 and 2, respectively (P >0.05). The severity and frequency of UI and its impact on QoL were evaluated by the ICIQ-Short Form, with scores of 6.9±6.26 in Group 1 and 7.0±5.12 in Group 2 (P >0.05). The IIEF-5 scores were similar in Groups 1 and 2 (5.73±7.43 vs. 6.70±6.68, respectively) (P >0.05). CONCLUSION: Our pre-RP protocol of two physical therapist-assisted sessions of PFMT plus instructions did not signifi cantly improve urinary continence or erectile function at 3 months after RP.
Assuntos
Disfunção Erétil/reabilitação , Exercícios de Alongamento Muscular/métodos , Diafragma da Pelve/fisiopatologia , Assistência Perioperatória/métodos , Prostatectomia/reabilitação , Incontinência Urinária/reabilitação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Gradação de Tumores , Estadiamento de Neoplasias , Neurorretroalimentação , Estudos Prospectivos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologiaRESUMO
ABSTRACT Aims: Radical prostatectomy (RP) can result in urinary incontinence (UI) and erectile dysfunction (ED), which negatively impact quality of life (QoL). This study aimed to evaluate the effects of a perioperative pelvic floor muscle training (PFMT) program versus usual care on early recovery of urinary continence and erectile function after RP. Materials and Methods: Of 59 eligible men, 31 were randomly allocated into 2 groups: Group 1 (Control, N=15) received usual post-RP care; and Group 2 (Physical therapy, N=16) received two pre-RP physical therapist-guided PFMT sessions, including exercises and electromyographic biofeedback, and verbal and written instructions to continue PFMT until RP, which was then resumed after urethral catheter removal. The International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire were used to evaluate UI and ED, respectively. Results: Demographic characteristics were similar in both groups. Three months after RP, the UI rate was 72.7% and 70.0% in Groups 1 and 2, respectively (P >0.05). The severity and frequency of UI and its impact on QoL were evaluated by the ICIQ-Short Form, with scores of 6.9±6.26 in Group 1 and 7.0±5.12 in Group 2 (P >0.05). The IIEF-5 scores were similar in Groups 1 and 2 (5.73±7.43 vs. 6.70±6.68, respectively) (P >0.05). Conclusion: Our pre-RP protocol of two physical therapist-assisted sessions of PFMT plus instructions did not significantly improve urinary continence or erectile function at 3 months after RP.
Assuntos
Humanos , Masculino , Idoso , Prostatectomia/reabilitação , Incontinência Urinária/reabilitação , Diafragma da Pelve/fisiopatologia , Assistência Perioperatória/métodos , Exercícios de Alongamento Muscular/métodos , Disfunção Erétil/reabilitação , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Qualidade de Vida , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Neurorretroalimentação , Gradação de Tumores , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Estadiamento de NeoplasiasRESUMO
Pumpkin seeds are often used in traditional medicine in the management of erectile dysfunction. However, there is insufficient information about the possible biochemical rationale behind this practice. Hence, this study investigated the influence of fluted pumpkin seed on critical enzymes involved in erectile function in isolated rats' corpus cavernosum in vitro. The phenolics and amino acid contents of fluted pumpkin seed were determined using HPLC-DAD and GC-PFPD analyses respectively. The aqueous extract of the fluted pumpkin seed significantly (p < .05) scavenged free radicals and inhibited PDE-5, arginase, AChE, and ACE in rats' corpus cavernosum in a concentration-dependent pattern. Quercitrin and luteolin were the most dominant phenolics, while arginine, aspartate, and cysteine were the most aboundant amino acid constituents. The positive modulatory effect of the fluted pumpkin seed on these critical markers of erectile function could be attributed to its polyphenolics and amino acid constituents. PRACTICAL APPLICATIONS: This study brought to limelight the medicinal importance of fluted pumpkin seed in erectile functions. Therefore, this seed could be used as a functional food ingredient in the management of erectile dysfunctions and also in improving erectile functions in men. In addition, the dominant phenolics and amino acid constituents of this seed might be an effective nutraceutical in enhancing erections in men.
Assuntos
Aminoácidos/metabolismo , Cucurbita/metabolismo , Disfunção Erétil/dietoterapia , Extratos Vegetais/metabolismo , Polifenóis/metabolismo , Aminoácidos/análise , Animais , Cucurbita/química , Disfunção Erétil/metabolismo , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Ereção Peniana , Pênis/fisiopatologia , Extratos Vegetais/análise , Polifenóis/análise , Ratos , Sementes/químicaRESUMO
ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.
Assuntos
Humanos , Animais , Masculino , Idoso , Pênis/efeitos dos fármacos , Acroleína/análogos & derivados , Óleos Voláteis/farmacologia , Cinnamomum zeylanicum/química , Relaxamento Muscular/efeitos dos fármacos , Pênis/fisiopatologia , Fenilefrina/farmacologia , Vasoconstritores/farmacologia , Acroleína/farmacologia , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Reprodutibilidade dos Testes , Análise de Variância , Ratos Sprague-Dawley , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Disfunção Erétil/fisiopatologia , Disfunção Erétil/tratamento farmacológico , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologiaRESUMO
Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.
Assuntos
Acroleína/análogos & derivados , Cinnamomum zeylanicum/química , Relaxamento Muscular/efeitos dos fármacos , Óleos Voláteis/farmacologia , Pênis/efeitos dos fármacos , Acroleína/farmacologia , Idoso , Análise de Variância , Animais , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologia , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Fenilefrina/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Citrato de Sildenafila/farmacologia , Vasoconstritores/farmacologiaAssuntos
Modelos Animais de Doenças , Disfunção Erétil/terapia , Perfilação da Expressão Gênica/métodos , Medicina Tradicional Chinesa/métodos , MicroRNAs/genética , Animais , Disfunção Erétil/genética , Disfunção Erétil/fisiopatologia , Masculino , Pênis/metabolismo , Pênis/fisiopatologia , Ratos , Ratos Sprague-Dawley , Comprimidos , Resultado do TratamentoRESUMO
BACKGROUND: Sexual problems are widespread and adversely affect the interpersonal relationships and the quality of life. Currently, synthetic drugs improving sexual function are available, but expenditures for such agents are extremely high. To discover relatively inexpensive, widely available and effective natural drugs, we identified a combined extracts from Lepidium meyenii (maca) root and Allium tuberosum Rottl. (Chinese chive) seed, assessed the effects of this combined extracts on erectile dysfunction, and explored its potential mechanisms. METHODS: The extracts were obtained via supercritical fluid extraction. Male BALB/c mice received doses of extract from single plant or the combined extracts (200 mg/kg) by gastric gavage for 14 d, and Viagra was used as the positive control drug. Sexual behaviour was observed, and concentrations of serum testosterone, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) in serum as well as in penis were measured. In addition, weights of genital organs were also measured. RESULTS: The combined extracts of maca root and Chinese chive seed (1:1, w/w) had a 45-fold increase in macamide content compared with maca extract. It also led to significantly higher ejaculation frequency (P < 0.05) than single extract from maca root or Chinese chive seed, with no corresponding effect on genital indices. In addition, the NO level in serum (P < 0.01) and penis (P < 0.05) increased notably, as well as the level of cGMP in penis (P < 0.05). CONCLUSIONS: The results indicated that the combined extracts produced better synergistic effects on male sexual function than maca extract or Chinese chive extract alone. These positive effects may involve the upregulation of NO and cGMP concentrations in penis.
Assuntos
Cebolinha-Francesa/química , Disfunção Erétil/tratamento farmacológico , Lepidium/química , Extratos Vegetais/administração & dosagem , Animais , Disfunção Erétil/sangue , Disfunção Erétil/fisiopatologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/fisiopatologia , Qualidade de Vida , Sementes/química , Comportamento Sexual Animal , Testosterona/sangueRESUMO
We used Box-Behnken design-based (BBD) response surface methodology (RSM) in this research to optimize the extraction process of Traditional medicine Majun Mupakhi Ela (MME) and evaluate its effect on hydrocortisone-induced kidney yang deficiency. Three independent parameters were applied to evaluate the maximum phosphodiesterase type 5 (PDE5) inhibition activity of MME extracts in vitro. The optimal processing conditions (extraction time 2 h, solid-liquid ratio 1:16, extraction once) gave a maximum PDE5 inhibition rate of 84.10%, flavonoid content of 0.49 mg/ml, icariin content of 0.028 mg/ml and targeted extraction yield of 26.50%. In animal experiments, MME extracts significantly increased the adrenal mass index, semen weight index, preputial gland weight index, and penis weight index in mice; in the middle and high dose group, the level of serum testosterone increased by 7664.29% and 14207.14% respectively, compared with the model group, and the level of PDE5 decreased by 67.22% and 74.69% respectively compared with the control group. These results indicate that MME has a significant positive effect on the hypothalamus-pituitary-gonadal axis, improve mating ability and not only has inhibits PDE5 activity but also significantly inhibits the expression of PDE5 in penile tissues, potential to become erectile dysfunction (ED) therapies for the clinical management of patients with kidney yang deficiency.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Animais , China , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Medicamentos de Ervas Chinesas/química , Disfunção Erétil/fisiopatologia , Hidrocortisona/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pênis/metabolismo , Inibidores da Fosfodiesterase 5/química , Inibidores da Fosfodiesterase 5/isolamento & purificação , Deficiência da Energia Yang/metabolismoRESUMO
Prostatism and erectile dysfunction (ED) are highly prevalent and closely comorbid. Prescription treatments are limitingly expensive but robust in mechanisms of action (MoA). Nutritional supplements (NS) are low-cost but inadequately supported by evidence. Do any NS use robust MoA? Could their efficacy be amplified via dosing, concentration of active principles, and/or use in combination? The goal is to develop an effective NS for prostatism and ED using the MoA of prescription treatments. Literature reviews were conducted on dietary supplements for prostatism or ED and MoA of relevant drugs. The most promising NS employing these MoA were chosen. A pilot study of a prototype combination was conducted. A protocol was created for an adequate dose-response trial to test the NS combination in men with ED and prostatism. The main measures were response rates, International Prostate Symptom Score, and International Index of Erectile Function. For drugs, the MoAs best proven for prostatism and ED were nitric oxide augmentation, mild androgen inhibition, and anti-inflammatory effects. The following NS best simulate these MoA and are best supported for efficacy; for prostatism: beta sitosterol; for ED: panax ginseng, arginine, and citrulline. Pilot clinical data provided support. A plan for a formal dose-response clinical trial was approved by a central institutional review board. NS using effective MoA might suffice for prostatism and ED. Pilot testing of a combination NS with the best-supported MoA supported further development. A dose-response trial should be conducted using adequate doses of L-citrulline, beta-sitosterol, ginseng, and vitamin D3.
Assuntos
Suplementos Nutricionais/análise , Disfunção Erétil/tratamento farmacológico , Prostatismo/tratamento farmacológico , Arginina/administração & dosagem , Colecalciferol/administração & dosagem , Citrulina/administração & dosagem , Ensaios Clínicos como Assunto , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Panax/química , Projetos Piloto , Extratos Vegetais/administração & dosagem , Prostatismo/fisiopatologia , Sitosteroides/administração & dosagem , Micção/efeitos dos fármacosRESUMO
INTRODUCTION: On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection. AIM: To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails. METHODS: PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy. MAIN OUTCOME MEASURES: The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD). RESULTS: Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy. Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an α1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED. CONCLUSION: For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an α1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment. Munk NE, Knudsen JS, Comerma-Steffensen S, et al. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019;7:430-441.
Assuntos
Alprostadil/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Ereção Peniana/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/efeitos adversos , Citrato de Sildenafila/administração & dosagem , Tadalafila/administração & dosagem , Administração Oral , Quimioterapia Combinada , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Falha de Tratamento , Resultado do Tratamento , Vasodilatadores/administração & dosagemRESUMO
OBJECTIVES: To compare monopolar transurethral resection of the prostate (TURP), bipolar TURP and photoselective vaporization of the prostate (PVP) by 120-W GreenLight laser with regard to the impact on International Index of Erectile Function (IIEF)-5 score in patients presenting with lower urinary tract symptoms (LUTS) secondary to prostate >80 mL. METHODS: Between April 2012 and March 2015, 110 patients who satisfied eligibility criteria were divided into three groups according to surgical modality adopted to treat benign prostatic enlargement. Preoperative, perioperative, and follow-up data were collected. The three groups were as follows: group A, monopolar TURP; group B, bipolar TURP; and group C, PVP. RESULTS: The baseline characteristics of the three groups were similar. All the perioperative parameters were significantly favorable in group C compared with the other two groups, except for mean operative time, which was significantly higher in group C. International Prostate Symptom Score, postvoid residual urine, maximum flow rate and quality of life score had significant and similar improvement during follow up in all three groups. Also, prostate volume reduced significantly in all three groups following surgery, but it remained significantly higher in group C patients compared with groups A and B. Mean IIEF-5 score was similar between the three groups at baseline and during each of the follow-up visits. Groups A, B and C had declines of 3.27% (P = 0.34), 2.68% (P = 0.40) and 3.36% (P = 0.35), respectively, in mean IIEF-5 score at 12-month follow up compared with baseline. CONCLUSIONS: Monopolar TURP, bipolar TURP and PVP by 120-W GreenLight laser for prostate size >80 mL do not have a significant impact on IIEF-5 score at 12-month follow up.
Assuntos
Disfunção Erétil/cirurgia , Terapia a Laser/métodos , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Idoso , Endoscopia/métodos , Disfunção Erétil/fisiopatologia , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: Erectile dysfunction (ED) is a common complication of diabetes. This study aimed to explore the beneficial effect of Danshen injection on ED in a streptozotocin (STZ)-induced diabetic rat model and the underlying mechanism. METHODS: The diabetic rat model was established by an intraperitoneal injection of 60 mg/kg STZ in male Sprague-Dawley rats. The diabetic rats were intraperitoneally injected with Danshen solution (0.5 or 1 mL/kg/day) or the same volume of saline for 6 weeks. Age-matched rats served as controls. After 6 weeks, erectile function and histological morphology of the corpora cavernosum were assessed. Oxidative stress indicators, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels, were measured in penile tissues. The expression levels of glucose-regulated protein 78 (Grp78), growth arrest and DNA damage-inducible gene 153 (GADD153/CHOP) were determined by immunohistochemistry, immunoblotting, and RT-PCR. Apoptosis was detected by a TUNEL assay. RESULTS: The erection times of diabetic rats were significantly less than those of control rats. Danshen injection could improve erectile function via increased erection times. Danshen injection was also found to ameliorate the morphological abnormalities of the corpora cavernosum, to reduce the number of apoptotic cells, and to suppress caspase-3 activation in penile tissue, accompanied by downregulation of the endoplasmic reticulum stress biomarkers Grp78 and CHOP. Danshen injection could increase SOD activity as well as reduce ROS and MDA levels in diabetic rats, indicating suppression of oxidative stress. CONCLUSION: Danshen injection could rescue diabetes-associated ED, possibly via suppressing the oxidative stress and endoplasmic reticulum (ER) stress-induced apoptosis pathways.
Assuntos
Complicações do Diabetes/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Disfunção Erétil/tratamento farmacológico , Salvia miltiorrhiza/química , Animais , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Chaperona BiP do Retículo Endoplasmático , Disfunção Erétil/metabolismo , Disfunção Erétil/fisiopatologia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/fisiologia , Humanos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
INTRODUCTION: We aimed to evaluate the effects of hyperbaric oxygen therapy (HBOT) on erectile function in patients who had no cavernosal or urethral injury by using International Index of Erectile Function (IIEF) questionnaire. MATERIALS AND METHODS: The male patients who were treated by HBOT for several diseases between July 2017 and September 2017 were examined. All patients filled the IIEF questionnaire form before the first day and after the last day of HBOT and a questionnaire including demographic characteristics and medical history. The effects of demographic characteristics and risk factors on erectile function were evaluated, and the IIEF domain scores of patients in first day and last day of HBOT were compared. RESULTS: Totally, 50 patients were included in the study between July 2017 and September 2017 and the mean age was 59.38 ± 13.77. The mean post-HBOT IIEF-EF score of patients was significantly higher than the mean pre-HBOT IIEF-EF score of patients (15.74 ± 10.52 vs. 19.50 ± 10.91; p < 0.001). The mean post-HBOT IIEF scores of other domains including intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction were also significantly higher than pre-HBOT scores. CONCLUSIONS: HBOT may be a good alternative treatment or adjunctive treatment for erectile dysfunction.
Assuntos
Disfunção Erétil/terapia , Oxigenoterapia Hiperbárica , Ereção Peniana , Idoso , Disfunção Erétil/diagnóstico , Disfunção Erétil/fisiopatologia , Disfunção Erétil/psicologia , Humanos , Oxigenoterapia Hiperbárica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Orgasmo , Satisfação do Paciente , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Comportamento Sexual , Resultado do TratamentoRESUMO
RELEVANCE: Erectile dysfunction (ED) is a common condition. Pharmacological management of ED involves medications produced by chemical synthesis. Despite high efficiency, their use is often accompanied by some side effects. Considering this, herbal preparations with sufficient efficacy and greater safety have received much attention. AIM: To compare the efficacy and safety of two herbal preparations (EFFEX Tribulus and Tribestan) based on Tribulus Terrestris herb dry extract in patients with ED. MATERIALS AND METHODS: A total of 173 patients were enrolled in the study, of whom 87 (group I) and 86 (group II) received EFFEX Tribulus and Tribestan, respectively. The mean age of patients was 42.2+/-11.5 years in group I and 42.8+/-11.2 years in group II. One hundred fifty two patients completed the study. The follow-up was 13 weeks (the herbal preparation dose was titrated at week five after the treatment initiation). The effectiveness of treatment was assessed on five follow-up visits using the IIEF, AMS, MSF, GAQ questionnaires, and a complex of diagnostic and laboratory studies. RESULTS: At visit five compared to visit 1, the mean IIEF erectile function domain score increased by 5.7+/-4.6 and 5.2+/-4.3 points in group I and II, respectively. In both groups, all other IIEF domain scores demonstrated a statistically significant increase. The AMS scores decreased from 32.93+/-10.04 to 25.02+/-7.62 points in group I and 31.78+/-10.37 to 24.55+/-7.31 points in group II. The SMF scores increased from 22.36+/-4.85 to 27.16+/-4.80 points in group I and from 22.13+/-3.69 to 26.10+/-5.69 points in group II. Besides, the use of the herbal preparations was associated with a decrease in the serum cholesterol level, more pronounced with increasing patient age (correlation coefficient -0.06, p=0.41). CONCLUSION: The herbal preparations EFFEX Tribulus and Tribestan have a similar efficacy and safety profiles.
Assuntos
Disfunção Erétil/tratamento farmacológico , Fitoterapia , Extratos Vegetais/administração & dosagem , Preparações de Plantas/administração & dosagem , Saponinas/administração & dosagem , Tribulus/química , Adulto , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Sexual health positively correlates with overall wellbeing. Existing therapeutics to enhance male sexual health are limited by factors that include responsiveness, adherence and adverse effects. As the population ages, safe and effective interventions that preserve male sexual function are needed. Published research suggests that various preparations of Kaempferia parviflora, a plant in the Zingiberaceae (ginger) family, support cardiovascular health and may ameliorate erectile function. OBJECTIVE: The aim of this study was to examine the effects of KaempMax™, an ethanol extract of the K. parviflora rhizome, on erectile function in healthy middle-aged and older men. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We conducted an open-label, one-arm study on 14 generally healthy males aged 50-68â¯years with self-reported mild erectile dysfunction, who were not using prescription treatments. Participants took 100â¯mg KaempMax™ daily for 30â¯days. MAIN OUTCOME MEASURES: Evaluations were conducted at baseline and on the final study assessment. Primary efficacy analyses included the International Index of Erectile Function (IIEF); secondary efficacy analyses included the Global Assessment Question about erectile function. RESULTS: Thirteen participants completed the 30-day study. Supplementation with KaempMax™ resulted in statistically significant improvements in erectile function, intercourse satisfaction and total scores on the IIEF questionnaire. KaempMax™ was well tolerated and exhibited an excellent safety profile. CONCLUSION: Our results suggest that KaempMax™ may improve erectile function in healthy middle-aged and older men. While the effects were not as pronounced as what might be seen with prescription medication, most participants found them satisfactory. Additional, longer and placebo-controlled clinical trials will be needed. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03389867.