{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T06:56:04Z","timestamp":1791701764692,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,9]],"date-time":"2020-08-09T00:00:00Z","timestamp":1596931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Type 5 phosphodiesterase inhibitor (PDE5I) has become the first\u2010line treatment for erectile dysfunction (ED). However, its effective rate for hypertension ED is only 60%\u201070%. How to improve the efficacy of ED treatment is the focus of current research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore whether icariin can improve the erectile function of spontaneously hypertensive rats (SHR) by affecting post\u2010translational protein\u2010protein interactions to regulate endothelial nitric oxide synthetase (eNOS) activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Twelve\u2010week\u2010old healthy male SHR rats and Wistar\u2010Kyoto rats (WKY) were randomly divided into four groups: SHR control group, SHR\u00a0+\u00a0icariin (10\u00a0mg\/kg\u00b7d gavage) treatment group, WKY control group, and WKY\u00a0+\u00a0icariin (10\u00a0mg\/kg\u00b7d gavage) treatment group (n\u00a0=\u00a05). After 4\u00a0weeks, the maximum penile intracavernous pressure\/mean arterial pressure (ICPmax\/MAP), the expression of heat\u2010shock protein 90 (Hsp90), caveolin\u20101, calmodulin, p\u2010eNOS, and eNOS in penile cavernous tissue and the content of nitric oxide (NO) and cGMP were measured. The interaction between eNOS and Hsp90, caveolin\u20101, and calmodulin were detected by immunoprecipitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>The ICPmax\/MAP in the SHR\u00a0+\u00a0icariin treatment group (0.08\u00a0\u00b1\u00a00.01, 0.23\u00a0\u00b1\u00a00.07, 0.40\u00a0\u00b1\u00a00.05) was significantly higher than the SHR group (0.03\u00a0\u00b1\u00a00.01, 0.13\u00a0\u00b1\u00a00.03, 0.21\u00a0\u00b1\u00a00.02) under 3V and 5V electrical stimulations (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Compared with the SHR group, the expression of HSP90, calmodulin, P\u2010eNOS, eNOS, and P\u2010eNOS\/eNOS in the penile cavernous tissue of rats in the WKY group and the SHR\u00a0+\u00a0icariin treatment group were significantly increased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05), and the expression of caveolin\u20101 was significantly decreased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). The NO content (2.16\u00a0\u00b1\u00a00.22\u00a0\u03bcmol\/g) and cGMP concentration (3.69\u00a0\u00b1\u00a00.12\u00a0pmol\/mg) in the SHR\u00a0+\u00a0icariin treatment group were significantly higher than those in the SHR group (1.01\u00a0\u00b1\u00a00.14\u00a0\u03bcmol\/g, 2.31\u00a0\u00b1\u00a00.22\u00a0pmol\/mg) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Compared with the SHR group, the interaction between eNOS and HSP90 in the cavernosa of the rats in the SHR\u00a0+\u00a0icariin treatment group was significantly increased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05), the interaction between eNOS and caveolin\u20101 was significantly decreased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01), and the interaction between eNOS and calmodulin did not significantly change.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and Conclusion<\/jats:title><jats:p>Up\u2010regulating the expression of HSP90 and calmodulin and inhibiting caveolin\u20101 in SHR corpus cavernosum, promoting the interaction between eNOS and HSP90, inhibiting the interaction between eNOS and caveolin\u20101, increasing p\u2010eNOS\/eNOS, may be the mechanism of icariin that improves SHR erectile function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12875","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T21:31:41Z","timestamp":1595885501000},"page":"342-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Icariin modulates eNOS activity via effect on post\u2010translational protein\u2010protein interactions to improve erectile function of spontaneously hypertensive rats"],"prefix":"10.1111","volume":"9","author":[{"given":"Qin\u2010Wen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology the Affiliated Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology the Affiliated Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery the Affiliated Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-3643","authenticated-orcid":false,"given":"Rui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology the Affiliated Hospital of Southwest Medical University Luzhou China"},{"name":"Nephropathy Clinical Medical Research Center of Sichuan Province Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2018.05.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1999.00142.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.13376"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.10824"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2019.10.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.154304"},{"issue":"10","key":"e_1_2_9_8_1","first-page":"1731","article-title":"Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta\u2010analysis","volume":"49","author":"Gong B","year":"2017","journal-title":"IntUrolNephrol"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X19500022"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2021-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2016.12.002"},{"issue":"10","key":"e_1_2_9_12_1","first-page":"1190","article-title":"Reciprocal regulation of eNOS and caveolin\u20101 functions in endothelial cells. 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