Icariin improves SHR erectile function via inhibiting eNOS uncoupling

Long, Heng; Jiang, Jun; Xia, Jianguo; Jiang, Rui

doi:10.1111/and.13084

Cited by 12 publications

(18 citation statements)

References 25 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The serum testosterone and body weight in the WKY group and the SHR + icariin treatment group were not significantly different from those in the SHR group, and the expressions of eNOS and ICPmax/MAP were significantly increased compared to the SHR group. Showing that icariin can improve the erectile function of SHR by up‐regulating eNOS expression without affecting testosterone levels is consistent with previous studies 23,24 …”

Section: Discussionsupporting

confidence: 90%

“…Showing that icariin can improve the erectile function of SHR by up-regulating eNOS expression without affecting testosterone levels is consistent with previous studies. 23,24 This study found that the expression of HSP90 and calmodulin in the WKY group and the SHR + icariin treatment group was significantly higher than in the SHR group, and the expression of caveolin-1 was markedly lower than in the SHR group. HSP90 acts as…”

Section: F I G U R Ementioning

confidence: 78%

“…26 Our previous research found that icariin can improve erectile function by inhibiting eNOS uncoupling, but the specific mechanism is unclear. 23 This study suggested that the up-regulation of HSP90 by icariin may be one of the mechanisms that inhibits eNOS uncoupling and improves SHR erectile function. 27 Calmodulin can directly bind and activate eNOS.…”

Section: F I G U R Ementioning

confidence: 90%

See 2 more Smart Citations

Icariin modulates eNOS activity via effect on post‐translational protein‐protein interactions to improve erectile function of spontaneously hypertensive rats

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Type 5 phosphodiesterase inhibitor (PDE5I) has become the first‐line treatment for erectile dysfunction (ED). However, its effective rate for hypertension ED is only 60%‐70%. How to improve the efficacy of ED treatment is the focus of current research. Objective To explore whether icariin can improve the erectile function of spontaneously hypertensive rats (SHR) by affecting post‐translational protein‐protein interactions to regulate endothelial nitric oxide synthetase (eNOS) activity. Method Twelve‐week‐old healthy male SHR rats and Wistar‐Kyoto rats (WKY) were randomly divided into four groups: SHR control group, SHR + icariin (10 mg/kg·d gavage) treatment group, WKY control group, and WKY + icariin (10 mg/kg·d gavage) treatment group (n = 5). After 4 weeks, the maximum penile intracavernous pressure/mean arterial pressure (ICPmax/MAP), the expression of heat‐shock protein 90 (Hsp90), caveolin‐1, calmodulin, p‐eNOS, and eNOS in penile cavernous tissue and the content of nitric oxide (NO) and cGMP were measured. The interaction between eNOS and Hsp90, caveolin‐1, and calmodulin were detected by immunoprecipitation. Result The ICPmax/MAP in the SHR + icariin treatment group (0.08 ± 0.01, 0.23 ± 0.07, 0.40 ± 0.05) was significantly higher than the SHR group (0.03 ± 0.01, 0.13 ± 0.03, 0.21 ± 0.02) under 3V and 5V electrical stimulations (P < .05). Compared with the SHR group, the expression of HSP90, calmodulin, P‐eNOS, eNOS, and P‐eNOS/eNOS in the penile cavernous tissue of rats in the WKY group and the SHR + icariin treatment group were significantly increased (P < .05), and the expression of caveolin‐1 was significantly decreased (P < .05). The NO content (2.16 ± 0.22 μmol/g) and cGMP concentration (3.69 ± 0.12 pmol/mg) in the SHR + icariin treatment group were significantly higher than those in the SHR group (1.01 ± 0.14 μmol/g, 2.31 ± 0.22 pmol/mg) (P < .05). Compared with the SHR group, the interaction between eNOS and HSP90 in the cavernosa of the rats in the SHR + icariin treatment group was significantly increased (P < .05), the interaction between eNOS and caveolin‐1 was significantly decreased (P < .01), and the interaction between eNOS and calmodulin did not significantly change. Discussion and Conclusion Up‐regulating the expression of HSP90 and calmodulin and inhibiting caveolin‐1 in SHR corpus cavernosum, promoting the interaction between eNOS and HSP90, inhibiting the interaction between eNOS and caveolin‐1, increasing p‐eNOS/eNOS, may be the mechanism of icariin that improves SHR erectile function.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: F I G U R Ementioning

confidence: 78%

Section: F I G U R Ementioning

confidence: 90%

See 1 more Smart Citation

Icariin modulates eNOS activity via effect on post‐translational protein‐protein interactions to improve erectile function of spontaneously hypertensive rats

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our previous study found that hypertension promoted the uncoupling of eNOS in rat corpus cavernosum and inhibited the erectile function of hypertensive rats 13 . Meanwhile, ED induced by type 2 diabetes, hypercholesterolemia, and age is characterized by increased eNOS uncoupling in the penile tissue, 14‐16 which indicates that the coupling state of eNOS plays an essential role in the process of penile erection.…”

Section: Introductionmentioning

confidence: 97%

“…[8][9][10] In the nicotinamide adenine dinucleotide phosphate oxidase (NOX) family which reflects the redox level in tissue, nicotinamide Our previous study found that hypertension promoted the uncoupling of eNOS in rat corpus cavernosum and inhibited the erectile function of hypertensive rats. 13 Meanwhile, ED induced by type 2 diabetes, hypercholesterolemia, and age is characterized by increased eNOS uncoupling in the penile tissue, [14][15][16] which indicates that the coupling state of eNOS plays an essential role in the process of penile erection. However, whether androgens affect the coupling of eNOS remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background The number of erectile dysfunction (ED) patients is increasing annually. How to improve the effectiveness of ED treatment is an important issue for the field of andrology. Objectives To investigate whether low androgen status impairs the erectile function of rats by regulated endothelial nitric oxide synthase (eNOS) uncoupling. Materials and methods Thirty‐six 8‐week‐old male Sprague Dawley (SD) rats were randomly divided into six groups as follows: 4‐week sham‐operated group (4w‐sham), 4‐week castration group (4w‐cast), 4‐week castration + testosterone (T) group (4w‐cast + T), 8‐week sham‐operated group (8w‐sham), 8‐week castration group (8w‐cast), and 8‐week castration + T group (8w‐cast + T). Three mg/kg of T was subcutaneously injected every other day in castration + T groups. The ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the level of serum T, dihydrobiopterin(BH2), tetrahydrobiopterin (BH4), nitric oxygen(NO), 3‐nitrotyrosine(3NT), dihydrofolate reductase (DHFR), guanosine triphosphate cyclohydrolase 1 (GTPCH1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and eNOS monomers/dimers in the corpus cavernosum were detected. Results The ratio of ICPmax/MAP and BH4/BH2, the level of serum T, NO, and GTPCH1 decreased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .05) and decreased significantly in 8w‐cast group compared with 4w‐cast group (P < .05). The expression of 3NT and NOX2 and the ratio of eNOS monomers/dimers increased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .01) and increased significantly in 8w‐cast group compared with 4w‐cast group (P < .01). The expression of DHFR in 4w‐cast group was significantly higher than that in 4w‐sham group and 4w‐cast + T group (P < .01) and in 8w‐cast group was significantly lower than that in 8w‐sham group and 8w‐cast + T group (P < .01). Discussion and Conclusion Low androgen status induces eNOS uncoupling by reducing BH4/BH2 and increasing 3NT. Due to the decreased NO production, the erectile function of the rats was impaired.

show abstract

Icariin alleviates high‐fat diet‐induced nonalcoholic fatty liver disease via up‐regulating miR‐206 to mediate NF‐κB and MAPK pathways

Zhao,

Tian

2023

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is an abnormal lipid accumulation disease in hepatocytes. The existing drugs for NAFLD have some side effects, so new therapeutic agents are required to be explored. In this study, the effect and mechanism of icariin (ICA) on high‐fat diet‐induced NAFLD were investigated. Firstly, a high‐fat diet was used to construct a NAFLD rat model and HepG2 cells were treated with 1 mM free fatty acid (FFA). After ICA treatment, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), triglyceride (TG), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) were measured; liver injury and lipid deposition were observed by H&E and Oil Red O staining; interleukin‐1β (IL‐1β), IL‐12, and IL‐6 were measured by enzyme‐linked immunosorbent assay. Additionally, qRT‐PCR and western blot were performed to detect miR‐206 expression and NF‐κB/MAPK pathway‐related protein expression in liver tissues and cells. After a variety of trials, we discovered that compared with the NAFLD group, ICA significantly reduced ALT, AST, TBil, TG, TC, and LDL‐C levels and increased HDL‐C levels, and improved liver tissue injury and lipid deposition. Moreover, ICA reduced IL‐1β, IL‐12, and IL‐6 levels in liver tissues and cells as well as inhibited MAPK and NF‐κB‐related protein expression in the liver tissues. Notably, ICA could significantly increase miR‐206 expression in liver tissues and cells. Further experiments confirmed that inhibition of miR‐206 was able to reverse the effect of ICA on NAFLD. In conclusion, ICA can alleviate NAFLD by upregulating miR‐206 to mediate NF‐κB and MAPK pathways.

show abstract

Icariin improves SHR erectile function via inhibiting eNOS uncoupling

Cited by 12 publications

References 25 publications

Icariin modulates eNOS activity via effect on post‐translational protein‐protein interactions to improve erectile function of spontaneously hypertensive rats

Icariin modulates eNOS activity via effect on post‐translational protein‐protein interactions to improve erectile function of spontaneously hypertensive rats

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

Icariin alleviates high‐fat diet‐induced nonalcoholic fatty liver disease via up‐regulating miR‐206 to mediate NF‐κB and MAPK pathways

Contact Info

Product

Resources

About