Long-term administration of resveratrol and MitoQ stimulates cavernosum antioxidant gene expression in a mouse castration model of erectile dysfunction

Pierre, Clifford J.; Azeez, Tooyib A.; Rossetti, Michael L.; Gordon, Bradley S.; Favor, Justin D. La

doi:10.1016/j.lfs.2022.121082

Cited by 10 publications

(6 citation statements)

References 53 publications

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“…NFE2L2 regulates genes containing antioxidant response elements in their promoters. Pharmaceutical research in ED found that NFE2L2 was a promising target by regulating oxidative stress and inflammatory response in treating ED ( Draganski et al, 2018 ; Pierre et al, 2022 ). Similarly, in a model of chronic nonbacterial prostatitis, NFE2L2 was involved in the process that tadalafil alleviated inflammation and oxidative stress in RWPE-1 cells ( Song et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Uncovering the genetic links of diabetic erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome

Yuan

Sun²,

Han³

et al. 2023

Front. Physiol.

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Background: Clinical associations between erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been noticed, but the common pathogenic mechanisms between them remain elusive. The aim of the study was to mine shared genetic alterations between ED and chronic prostatitis/chronic pelvic pain syndrome.Method: Transcriptome data of ED and chronic prostatitis/chronic pelvic pain syndrome-related genes (CPRGs) were retrieved from relevant databases and differentially expressed analysis was used to obtain significant CPRGs. Then function enrichment and interaction analyses were performed to show shared transcriptional signature, including gene ontology and pathway enrichment, the construction of protein-protein interaction (PPI) network, cluster analysis, and co-expression analysis. Hub CPRGs and key cross-link were selected by validating these genes in clinical samples, chronic prostatitis/chronic pelvic pain syndrome and ED-related datasets. Then the miRNA-OSRGs co-regulatory network was predicted and validated. Subpopulation distribution and disease association of hub CPRGs were further identified.Result: Differentially expressed analysis revealed 363 significant CPRGs between ED and chronic prostatitis/chronic pelvic pain syndrome, functioning in inflammatory reaction, oxidative stress, apoptosis, smooth muscle cell proliferation, and extracellular matrix organization. A PPI network containing 245 nodes and 504 interactions was constructed. Module analysis depicted that multicellular organismal process and immune metabolic process were enriched. 17 genes were screened in PPI via topological algorithms, and reactive oxygen species as well as interleukin-1 metabolism were regarded as the bridging interactive mechanism. After screening and validation, a hub-CPRG signature consisting of COL1A1, MAPK6, LPL, NFE2L2 and NQO1 were identified and associated miRNA were verified. These miRNAs played an important role in immune and inflammatory response likewise. Finally, NQO1 was identified as a key genetic link between ED and chronic prostatitis/chronic pelvic pain syndrome. It was predominately enriched in corpus cavernosum endothelial cell, and correlated with other male urogenital and immune system diseases tightly.Conclusion: We identified the genetic profiles as well as corresponding regulatory network underlying interaction between ED and chronic prostatitis/chronic pelvic pain syndrome via multi-omics analysis. These findings expanded a new understanding for the molecular mechanism of ED with chronic prostatitis/chronic pelvic pain syndrome.

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Section: Discussionmentioning

confidence: 99%

Uncovering the genetic links of diabetic erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome

Yuan

Sun²,

Han³

et al. 2023

Front. Physiol.

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“…Regarding RESV’s ability to promote health benefits through its role in activating Nrf2, several experimental studies have been conducted in this context; the vast majority of these studies were carried out in vivo ( Table 1 ) and in vitro ( Table 2 ), but some randomized clinical trials were also reported ( Table 3 ) [ 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 ,…”

Section: Stilbenes: Compounds-based Approachmentioning

confidence: 99%

E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway

Mendonça,

Xavier,

Fragoso

et al. 2024

Pharmaceuticals

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Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative route (in microorganism cultures). The latter is a metabolic engineering strategy to enhance production due to stilbenes recognized pharmacological and medicinal potential. It is believed that in the human body, these potential activities can be modulated by the regulation of the nuclear factor erythroid derived 2 (Nrf2), which increases the expression of antioxidant enzymes. Given this, our review aims to critically analyze evidence regarding E-stilbenes in human metabolism and the Nrf2 activation pathway, with an emphasis on inflammatory and oxidative stress aspects related to the pathophysiology of chronic and metabolic diseases. In this comprehensive literature review, it can be observed that despite the broad number of stilbenes, those most frequently explored in clinical trials and preclinical studies (in vitro and in vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, and pinosylvin. In some cases, depending on the dose/concentration and chemical nature of the stilbene, it was possible to identify activation of the Nrf2 pathway. Furthermore, the use of some experimental models presented a challenge in comparing results. In view of the above, it can be suggested that E-stilbenes have a relationship with the Nrf2 pathway, whether directly or indirectly, through different biological pathways, and in different diseases or conditions that are mainly related to inflammation and oxidative stress.

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“…Only some of these compounds have been studied in in vitro settings and in vivo in a few animal species, revealing complex physicochemical and pharmacokinetic profiles that make their use in humans challenging. This justifies, in part, the absence of arginases inhibitors in clinical practice and reveals that more studies, at least with the most active compounds, are required to determine how they inhibit the activity of the two arginases in order to identify the doses and routes of administration to be tested in vascular pathologies, including ED, as has been done with other polyphenols (resveratrol and quercetin) in cardiovascular diabetology [88][89][90].…”

Section: Arginasementioning

confidence: 99%

“…As these enzymes convert L-arginine to urea and L-ornithine and compete with NO synthases for L-arginine [76], they are a target for the therapy of vascular ED, as found in diabetes and atherosclerosis [76,80,81]. However, although several arginase inhibitors are available [38,87], doses and administration routes have yet to be identified to test these compounds in vascular pathologies including ED, as has already been done with other polyphenols in cardiovascular diabetology [88][89][90].…”

Section: Final Remarksmentioning

confidence: 99%

Erectile Dysfunction: Treatments, Advances and New Therapeutic Strategies

Argiolas

et al. 2023

Brain Sciences

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Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men’s life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D4 receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients.

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Long-term administration of resveratrol and MitoQ stimulates cavernosum antioxidant gene expression in a mouse castration model of erectile dysfunction

Cited by 10 publications

References 53 publications

Uncovering the genetic links of diabetic erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome

Uncovering the genetic links of diabetic erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome

E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway

Erectile Dysfunction: Treatments, Advances and New Therapeutic Strategies

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