Restorative effect of resveratrol on expression of endothelial and neuronal nitric oxide synthase in cavernous tissues of chronic unpredictable mild stress-exposed rats: an impact of inflammation

Yazır, Yusufhan; Şahin, Tuğçe Demirtaş; Rençber, Selenay Furat; Gacar, Gülçin; Halbutoğulları, Zehra Seda; Utkan, Tijen; Arıcıoğlu, Feyza

doi:10.1038/s41443-018-0048-0

Cited by 20 publications

(8 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…50 Long-term chronic inflammation and the release of inflammatory factors downregulate eNOS and lead to a decrease in NO bioavailability. 51,52 In the current research, our data revealed that the beneficial effects of Pae application on erectile function may Cavernous fibrosis is a serious morphological change of DMED. 25 Several previous studies have proven that fibrotic levels in CC of DMED are accompanied by profibrotic factor releasement, smooth muscle reduction, and excessive collagen production.…”

Section: Discussionmentioning

confidence: 51%

“…A cascade of reactions is then triggered, causing an erection of the penis 50 . Long‐term chronic inflammation and the release of inflammatory factors downregulate eNOS and lead to a decrease in NO bioavailability 51,52 . In the current research, our data revealed that the beneficial effects of Pae application on erectile function may include upregulation of the eNOS/NO/cGMP signaling pathway.…”

Section: Discussionmentioning

confidence: 58%

See 1 more Smart Citation

Paeonol ameliorates diabetic erectile dysfunction by inhibiting HMGB1/RAGE/NF‐kB pathway

Sun

Wang

et al. 2022

Andrology

View full text Add to dashboard Cite

Background:The management of diabetes mellitus-induced erectile dysfunction (DMED) is progressively becoming tricky due to the surge in the number of patients and the poor efficiency of phosphodiesterase type 5 inhibitors in DMED. Paeonol (Pae), as a traditional Chinese medicine, has been more and more widely used in the treatment of diabetic complications. However, whether Pae could be a potential therapeutic drug of DMED needs to be further evaluated. Objectives:To investigate the pharmacological effect and possible mechanism of Pae in the treatment of DMED.Methods: Intraperitoneal streptozotocin injection and an apomorphine test were used to construct the model of DMED. Seventeen DMED rats were divided into two groups: DMED group (n = 8) and DMED+Pae group (Pae; 100 mg/kg/d; oral administration; n = 9). In addition, there were still 10 normal age-matched male rats as control group.Four weeks later, the cavernous nerve electric stimulation was carried out to measure the erectile response. Moreover, the corpus cavernosum smooth muscle cells (CCSMCs) were primarily isolated and exposed to high glucose (HG) stimulation, Pae treatment and glycyrrhizin (GL; the selective inhibitor of HMGB1). After an incubation for 1 week, the CCSMCs were harvested for detection. Results:The impairment of erectile function was observed in DMED rats compared with control samples, accompanied by the upregulation of HMGB1/RAGE/NF-κB Pathway. The lower nitric oxide and cGMP level and the higher level of inflammation, fibrosis, and apoptosis were also observed in DMED rats. It showed contrast that Pae treatment could improve the erectile function, as well as histologic alteration and related molecular changes. In addition, Pae could downregulate the HMGB1/RAGE/NF-κB pathway to regulate the apoptosis and inflammation levels of CCSMCs in high-glucose conditions, which is similar to the results of GL treatment. Conclusion:Pae alleviated ED in DMED rats, likely by inhibiting HMGB1/RAGE/NF-κB Pathway, inflammatory, apoptosis, and fibrotic activity, and moderating endothelial dysfunction. Our study provide evidence for a potential new therapy for DMED.

show abstract

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 58%

Paeonol ameliorates diabetic erectile dysfunction by inhibiting HMGB1/RAGE/NF‐kB pathway

Sun

Wang

et al. 2022

Andrology

View full text Add to dashboard Cite

show abstract

“…The mRNA expressions of inflammation factors are correlated with the serum and protein levels in the CC. 34 EPL administration suppressed these factors to maintain low serum ADMA levels despite the high salt intake.…”

Section: Discussionmentioning

confidence: 99%

High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure

Kishimoto

Kataoka

Yamamoto

et al. 2020

The Journal of Sexual Medicine

View full text Add to dashboard Cite

Background: High salt intake is a risk factor for hypertension, which can potentially lead to erectile dysfunction (ED); however, the underlying pathological mechanisms remain unclear. Aim: To investigate whether erectile function is directly impaired by high salt intake and whether selective inhibition of mineralocorticoid receptor (MR) could provide protection from ED. Methods: 6-week-old male Dahl salt-sensitive rats were randomly divided into 3 groups: normal diet (0.3% NaCl; control, n ¼ 8), high-salt diet (8% NaCl; HS, n ¼ 8), and high-salt diet plus eplerenone (HS þ EPL, n ¼ 11). HS þ EPL rats were orally administered daily doses of EPL (75 mg/kg) for 6 weeks; control and HS rats received purified water on the same schedule. Outcomes: At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure and mean arterial pressure after cavernous nerve stimulation. Serum levels of asymmetric dimethylarginine and L-arginine were determined using ultraperformance liquid chromatographyetandem mass spectrometry. Quantitative PCR was used to assess the expression of MR, inflammation, and oxidative stress markers (nicotinamide adenine dinucleotide phosphate oxidase-1/4, p22 phox , interleukin-6, and superoxide dismutase-1), and protein arginine N-methyltransferase-1. Results: The intracavernosal pressure/mean arterial pressure ratio was significantly lower, whereas systolic blood pressure, MR expression, serum asymmetric dimethylarginine levels, oxidative stress, and levels of inflammatory biomarkers were significantly higher in HS rats than in control rats (P < .05). EPL administration significantly improved each of these parameters except systolic blood pressure and MR expression. No significant intergroup differences were observed for L-arginine and superoxide dismutase-1 levels. Clinical Translation: Our results provide a rationale for the need of salt restriction and the use of selective MR inhibitors in prophylaxis or treatment of ED in men consuming a high-salt diet. Strengths & Limitations: We are the first to report that the adverse impact of high salt intake on erectile function is mediated via MR activation, independent of its effect on blood pressure. A major limitation of this study is that responses of salt-resistant rats were not studied. Conclusions: High salt intake directly impaired erectile function in Dahl salt-sensitive rats, whereas selective MR inhibition ameliorated this effect. Kishimoto T, Kataoka T, Yamamoto Y, et al. High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure.

show abstract

“…Resveratrol could regulate the inflammation process induced by various stimuli and in different experimental models ( 20 ). Resveratrol could relieve the inflammatory process by reducing the cytokines, such as CRP, TNFα, IL-6, and MCP-1 ( 21 - 23 ).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol affects the migration and apoptosis of monocytes by blocking HMGB1/NF-κB pathway

Zhang¹,

Dong²,

Liu³

et al. 2021

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: Chronic inflammation is now recognized as a causal factor of aging. Resveratrol is a nonflavonoid compound that widely exists in plant species, exerting anti-inflammatory effects in vitro and in animal models. The chemotaxis of inflammatory cells and secretion of cytokines are key characters in inflammation response.Methods: The effects of lipopolysaccharide (LPS) and high mobility group box-1 (HMGB1) chromosomal on the migration, inflammatory response, and apoptosis of monocytes were detected. THP-1 cells were used to study the effects of resveratrol treatment on LPS-and HMGB-induced monocytes. We aimed to investigate the effect of Resveratrol on monocyte migration and the expression of a special cytokine named HMGB1 in THP-1 cells.Results: Resveratrol obviously inhibited THP-1 migration induced by LPS. LPS increased the expression of HMGB1 and its release in THP-1 cells, which were both decreased by resveratrol. Resveratrol inhibited the activity of NF-κB-p65 and the translocation of NF-κB-p65 from nucleus to cytoplasm induced by LPS.In addition, Resveratrol increased LPS and HMGB1-inhibited monocyte apoptosis. Resveratrol inhibited the LPS-induced HMGB1 secretion and its activation through NF-κB pathway. The THP-1 migration induced by LPS was inhibited by resveratrol.Conclusions: Resveratrol may inhibit monocyte migration and induce apoptosis by blocking downstream HMGB1/NF-κB/MCP-1 signaling pathways, thereby reducing systemic inflammation.

show abstract

Restorative effect of resveratrol on expression of endothelial and neuronal nitric oxide synthase in cavernous tissues of chronic unpredictable mild stress-exposed rats: an impact of inflammation

Cited by 20 publications

References 68 publications

Paeonol ameliorates diabetic erectile dysfunction by inhibiting HMGB1/RAGE/NF‐kB pathway

Paeonol ameliorates diabetic erectile dysfunction by inhibiting HMGB1/RAGE/NF‐kB pathway

High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure

Resveratrol affects the migration and apoptosis of monocytes by blocking HMGB1/NF-κB pathway

Contact Info

Product

Resources

About