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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.

Titel:	Icariin modulates eNOS activity via effect on post-translational protein-protein interactions to improve erectile function of spontaneously hypertensive rats.
Autor/in / Beteiligte Person:	Liu, QW ; Yang, ZH ; Jiang, J ; Jiang, R
Link:	Zum Volltext
Zeitschrift:	Andrology, Jg. 9 (2021), Heft 1, S. 342-351
Veröffentlichung:	Oxford : Wiley-Blackwell, 2013-, 2021
Medientyp:	academicJournal
ISSN:	2047-2927 (electronic)
DOI:	10.1111/andr.12875
Schlagwort:	Animals Calmodulin metabolism Caveolin 1 metabolism Drug Evaluation, Preclinical Drugs, Chinese Herbal pharmacology Epimedium Erectile Dysfunction enzymology Flavonoids pharmacology HSP90 Heat-Shock Proteins metabolism Male Penis enzymology Phytotherapy Random Allocation Rats, Inbred SHR Rats, Inbred WKY Rats Drugs, Chinese Herbal therapeutic use Erectile Dysfunction drug therapy Flavonoids therapeutic use Nitric Oxide Synthase Type III metabolism Penis drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Andrology] 2021 Jan; Vol. 9 (1), pp. 342-351. <i>Date of Electronic Publication: </i>2020 Aug 09. MeSH Terms: Drugs, Chinese Herbal / therapeutic use ; Erectile Dysfunction / drug therapy ; Flavonoids / therapeutic use ; Nitric Oxide Synthase Type III / metabolism ; Penis / *drug effects ; Animals ; Calmodulin / metabolism ; Caveolin 1 / metabolism ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal / pharmacology ; Epimedium ; Erectile Dysfunction / enzymology ; Flavonoids / pharmacology ; HSP90 Heat-Shock Proteins / metabolism ; Male ; Penis / enzymology ; Phytotherapy ; Random Allocation ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats References: Burnett AL, Nehra A, Breau RH, et al. Erectile dysfunction: AUA Guideline. J Urol. 2018;200(3):633‐641. ; Ayta IA, McKinlay JB, Krane RJ. 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Apolipoprotein E enhances endothelial‐NO production by modulating caveolin 1 interaction with endothelial NO synthase. Hypertension. 2012;60(4):1040‐1046. ; Jiang R, Chen JH, Jin J, Shen W, Li QM. Ultrastructural comparison of penile cavernous tissue between hypertensive and normotensive rats. Int J Impot Res. 2005;17(5):417‐423. Contributed Indexing: Keywords: Icariin; eNOS; protein‐protein interaction; spontaneous hypertension rat Substance Nomenclature: 0 (Calmodulin) ; 0 (Caveolin 1) ; 0 (Drugs, Chinese Herbal) ; 0 (Flavonoids) ; 0 (HSP90 Heat-Shock Proteins) ; EC 1.14.13.39 (Nitric Oxide Synthase Type III) ; EC 1.14.13.39 (Nos3 protein, mouse) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210128 Date Completed: 20211101 Latest Revision: 20240226 Update Code: 20240226

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