{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:28:39Z","timestamp":1786728519542,"version":"build-2736575974"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Erectile dysfunction is a complex and prevalent complication of diabetes, and effective treatments are lacking. Oxidative stress, fibrosis, and apoptosis are closely associated with the development of diabetes mellitus-related erectile dysfunction (DMED). Notably, ginsenoside Rb1 (Rb1) exerts antioxidant effects and displays promise in the treatment of DMED. This study evaluated the therapeutic efficacy of Rb1 in a rodent streptozotocin-induced DMED model. Thirty-two rats were randomly assigned to three groups: control group, DMED group, and DMED + Rb1 group. DMED was induced in male rats via an intraperitoneal injection of streptozotocin. After 8 weeks of Rb1 gavage, erectile function was assessed by the electrical stimulation of the cavernous nerve. In addition, western blot, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Masson\u2019s trichrome staining were performed to verify the relevant factors and protein expression. Rb1 effectively improved the erectile function of the corpus cavernosum, decreased collagen content, and increased smooth muscle content in rats with diabetes. Rb1 decreased the levels of the pro-inflammatory factors (interleukin [IL]-6, tumor necrosis factor alpha [TNF-\u03b1], and IL-1\u03b2), and increased the levels of the anti-inflammatory factors (IL-10 and IL-4). Moreover, the activities of superoxide dismutase and catalase and levels of nitric oxide (NO) were increased, whereas malondialdehyde activity was decreased. Additionally, Rb1 activated the phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (AKT)\/endothelial nitric oxide synthase (eNOS) signaling pathway and inhibited cell apoptosis. Rb1 can improve erectile function in rats with DMED by increasing the activity of the PI3K\/AKT\/eNOS pathway, reducing oxidative stress, inhibiting inflammation and apoptosis, and alleviating corpus cavernosum fibrosis.<\/jats:p>","DOI":"10.4103\/aja202528","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T13:00:19Z","timestamp":1754398819000},"page":"57-63","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Ginsenoside Rb1 mitigates diabetes-induced erectile dysfunction in rats by reducing oxidative stress and modulating the PI3K\/AKT\/eNOS pathway"],"prefix":"10.4103","volume":"28","author":[{"given":"Zong-Hai","family":"Liu","sequence":"first","affiliation":[{"name":"Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Bo","family":"Chen","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, The Second Hospital of Shandong University, Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, The Second Hospital of Shandong University, Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong-Zhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Pan","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Zhen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"R1-20260122","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.pop.2019.02.006","article-title":"Erectile dysfunction","volume":"46","author":"Irwin","year":"2019","journal-title":"Prim Care"},{"key":"R2-20260122","doi-asserted-by":"crossref","first-page":"108288","DOI":"10.1016\/j.jdiacomp.2022.108288","article-title":"Urologic complications in diabetes","volume":"36","author":"Blair","year":"2022","journal-title":"J Diabetes Complications"},{"key":"R3-20260122","doi-asserted-by":"crossref","first-page":"e3494","DOI":"10.1002\/dmrr.3494","article-title":"Erectile dysfunction and diabetes:a melting pot of circumstances and treatments","volume":"38","author":"Defeudis","year":"2022","journal-title":"Diabetes Metab Res Rev"},{"key":"R4-20260122","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2164\/jandrol.108.006106","article-title":"Erectile dysfunction management for the future","volume":"30","author":"Burnett","year":"2009","journal-title":"J Androl"},{"key":"R5-20260122","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11154-015-9321-4","article-title":"Erectile dysfunction and its management in patients with diabetes mellitus","volume":"16","author":"Defeudis","year":"2015","journal-title":"Rev Endocr Metab Disord"},{"key":"R6-20260122","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1111\/j.1743-6109.2012.02787.x","article-title":"Dropout in the treatment of erectile dysfunction with PDE5:a study on predictors and a qualitative analysis of reasons for discontinuation","volume":"9","author":"Carvalheira","year":"2012","journal-title":"J Sex Med"},{"key":"R7-20260122","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2174\/157016109788340767","article-title":"Ginseng compounds:an update on their molecular mechanisms and medical applications","volume":"7","author":"Lv","year":"2009","journal-title":"Curr Vasc Pharmacol"},{"key":"R8-20260122","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jvs.2005.01.054","article-title":"Ginsenoside Rb1 blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries","volume":"41","author":"Zhou","year":"2005","journal-title":"J Vasc Surg"},{"key":"R9-20260122","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/FJC.0b013e3180cab12e","article-title":"Protective effects of ginsenoside Rb1 on human umbilical vein endothelial cells in vitro","volume":"50","author":"He","year":"2007","journal-title":"J Cardiovasc Pharmacol"},{"key":"R10-20260122","doi-asserted-by":"crossref","first-page":"104109","DOI":"10.1016\/j.micpath.2020.104109","article-title":"Ginsenoside Rb 1:a novel therapeutic agent in Staphylococcus aureus-induced acute lung injury with special reference to oxidative stress and apoptosis","volume":"143","author":"Shaukat","year":"2020","journal-title":"Microb Pathog"},{"key":"R11-20260122","doi-asserted-by":"crossref","first-page":"112333","DOI":"10.1016\/j.ecoenv.2021.112333","article-title":"Ginsenoside Rb1 prevents deoxynivalenol-induced immune injury via alleviating oxidative stress and apoptosis in mice","volume":"220","author":"Rajput","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"R12-20260122","first-page":"3633","article-title":"Ginsenoside Rb1 attenuates intestinal ischemia\/reperfusion-induced inflammation and oxidative stress via activation of the PI3K\/Akt\/Nrf2 signaling pathway","volume":"19","author":"Chen","year":"2019","journal-title":"Mol Med Rep"},{"key":"R13-20260122","doi-asserted-by":"crossref","first-page":"101469","DOI":"10.1016\/j.mcp.2019.101469","article-title":"Ginsenoside Rb1 mitigates oxidative stress and apoptosis induced by methylglyoxal in SH-SY5Y cells via the PI3K\/Akt pathway","volume":"48","author":"Nan","year":"2019","journal-title":"Mol Cell Probes"},{"key":"R14-20260122","doi-asserted-by":"crossref","first-page":"753881","DOI":"10.3389\/fphar.2021.753881","article-title":"Ginsenoside Rb1 ameliorates diabetic arterial stiffening via AMPK pathway","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Pharmacol"},{"key":"R15-20260122","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.1007\/s11033-010-0558-4","article-title":"Protective effect of ginsenoside Rb1 against myocardial ischemia\/reperfusion injury in streptozotocin-induced diabetic rats","volume":"38","author":"Wu","year":"2011","journal-title":"Mol Biol Rep"},{"key":"R16-20260122","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3390\/antiox12010171","article-title":"Engineered adipose-derived stem cells overexpressing RXFP1 via CRISPR activation ameliorate erectile dysfunction in diabetic rats","volume":"12","author":"Sun","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"R17-20260122","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1001\/jama.2016.12284","article-title":"Erectile dysfunction","volume":"316","author":"Najari","year":"2016","journal-title":"JAMA"},{"key":"R18-20260122","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0022-5347(05)67900-1","article-title":"Incidence of erectile dysfunction in men 40 to 69 years old:longitudinal results from the Massachusetts male aging study","volume":"163","author":"Johannes","year":"2000","journal-title":"J Urol"},{"key":"R19-20260122","doi-asserted-by":"crossref","first-page":"8807","DOI":"10.3390\/cimb46080521","article-title":"Oxidative stress and erectile dysfunction:pathophysiology, impacts, and potential treatments","volume":"46","author":"Kaltsas","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"R20-20260122","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2174\/157489007780832579","article-title":"Targets for the treatment of erectile dysfunction:is NO\/cGMP still the answer?","volume":"2","author":"Leite","year":"2007","journal-title":"Recent Pat Cardiovasc Drug Discov"},{"key":"R21-20260122","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.2174\/138161205774913381","article-title":"The nitric oxide signaling pathway in the penis","volume":"11","author":"Burnett","year":"2005","journal-title":"Curr Pharm Des"},{"key":"R22-20260122","doi-asserted-by":"crossref","first-page":"116249","DOI":"10.1016\/j.jep.2023.116249","article-title":"Fermented Gynochthodes officinalis (F. C. How) Razafim. &B. Bremer alleviates diabetic erectile dysfunction by attenuating oxidative stress and regulating PI3K\/Akt\/eNOS pathway","volume":"307","author":"Liu","year":"2023","journal-title":"J Ethnopharmacol"},{"key":"R23-20260122","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s11010-013-1592-z","article-title":"Apolipoprotein A-I mimetic peptide reverse D-4F improves the biological functions of mouse bone marrow-derived late EPCs via PI3K\/AKT\/eNOS pathway","volume":"377","author":"Yang","year":"2013","journal-title":"Mol Cell Biochem"},{"key":"R24-20260122","doi-asserted-by":"crossref","first-page":"116987","DOI":"10.1016\/j.biopha.2024.116987","article-title":"Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the PI3K\/AKT\/eNOS signaling pathway","volume":"177","author":"Mao","year":"2024","journal-title":"Biomed Pharmacother"},{"key":"R25-20260122","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.vph.2011.12.006","article-title":"Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation","volume":"56","author":"Pan","year":"2012","journal-title":"Vascul Pharmacol"},{"key":"R26-20260122","doi-asserted-by":"crossref","first-page":"e201900201","DOI":"10.1590\/s0102-8650201900201","article-title":"Ginsenoside Rb1 attenuates diabetic retinopathy in streptozotocin-induced diabetic rats1","volume":"34","author":"Dong","year":"2019","journal-title":"Acta Cir Bras"},{"key":"R27-20260122","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/andr.13296","article-title":"Saxagliptin alleviates erectile dysfunction through increasing stromal cell-derived factor-1 in diabetes mellitus","volume":"11","author":"Sun","year":"2023","journal-title":"Andrology"},{"key":"R28-20260122","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S0022-5347(17)38543-9","article-title":"The characterization of a bio-assay of erectile function in a rat model","volume":"145","author":"Heaton","year":"1991","journal-title":"J Urol"},{"key":"R29-20260122","doi-asserted-by":"crossref","first-page":"e0306926","DOI":"10.1371\/journal.pone.0306926","article-title":"Therapeutic potential of salidroside in type I diabetic erectile dysfunction:attenuation of oxidative stress and apoptosis via the Nrf2\/HO-1 pathway","volume":"19","author":"Li","year":"2024","journal-title":"PLoS One"},{"key":"R30-20260122","doi-asserted-by":"crossref","first-page":"982","DOI":"10.21037\/tau-22-428","article-title":"Ganoderma lucidum polysaccharide ameliorated diabetes mellitus-induced erectile dysfunction in rats by regulating fibrosis and the NOS\/ERK\/JNK pathway","volume":"11","author":"Yao","year":"2022","journal-title":"Transl Androl Urol"},{"key":"R31-20260122","doi-asserted-by":"crossref","first-page":"9051426","DOI":"10.1155\/2016\/9051426","article-title":"Experimental diabetes mellitus in different animal models","volume":"2016","author":"Al-Awar","year":"2016","journal-title":"J Diabetes Res"},{"key":"R32-20260122","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1517\/14712598.2013.847085","article-title":"Stem-cell therapy for erectile dysfunction","volume":"13","author":"Lin","year":"2013","journal-title":"Expert Opin Biol Ther"},{"key":"R33-20260122","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jsxm.2016.11.314","article-title":"Intracavernous injection of human umbilical cord blood mononuclear cells improves erectile dysfunction in streptozotocin-induced diabetic rats","volume":"14","author":"Cengiz","year":"2017","journal-title":"J Sex Med"},{"key":"R34-20260122","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1142\/S0192415X19500496","article-title":"Antidiabetic potential of flavonoids from traditional Chinese medicine:a review","volume":"47","author":"Bai","year":"2019","journal-title":"Am J Chin Med"},{"key":"R35-20260122","doi-asserted-by":"crossref","first-page":"4520","DOI":"10.3390\/nu13124520","article-title":"Efficacy evaluation of plant products in the treatment of erectile dysfunction related to diabetes","volume":"13","author":"Nobili","year":"2021","journal-title":"Nutrients"},{"key":"R36-20260122","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41401-021-00788-0","article-title":"Ginsenoside Rb1 alleviates diabetic kidney podocyte injury by inhibiting aldose reductase activity","volume":"43","author":"He","year":"2022","journal-title":"Acta Pharmacol Sin"},{"key":"R37-20260122","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1080\/13880209.2022.2140168","article-title":"Ginsenoside Rb1 reduces oxidative\/carbonyl stress damage and ameliorates inflammation in the lung of streptozotocin-induced diabetic rats","volume":"60","author":"Su","year":"2022","journal-title":"Pharm Biol"},{"key":"R38-20260122","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3892\/mmr.2023.13052","article-title":"Pyroptosis and inflammation-mediated endothelial dysfunction may act as key factors in the development of erectile dysfunction (review)","volume":"28","author":"Zhu","year":"2023","journal-title":"Mol Med Rep"},{"key":"R39-20260122","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.yrtph.2004.08.004","article-title":"Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose","volume":"40","author":"Contrera","year":"2004","journal-title":"Regul Toxicol Pharmacol"},{"key":"R40-20260122","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1111\/jcmm.17394","article-title":"N-acetylcysteine improves diabetic associated erectile dysfunction in streptozotocin-induced diabetic mice by inhibiting oxidative stress","volume":"26","author":"Ma","year":"2022","journal-title":"J Cell Mol Med"},{"key":"R41-20260122","first-page":"544","article-title":"Oxidative stress and visual system:a review","volume":"21","author":"Taurone","year":"2022","journal-title":"EXCLI J"},{"key":"R42-20260122","doi-asserted-by":"crossref","first-page":"114606","DOI":"10.1016\/j.biopha.2023.114606","article-title":"Cellular Red-Ox system in health and disease:the latest update","volume":"162","author":"Jena","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"R43-20260122","doi-asserted-by":"crossref","first-page":"102852","DOI":"10.1016\/j.redox.2023.102852","article-title":"Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2\/HO-1 pathway in MCAO mice","volume":"66","author":"Sun","year":"2023","journal-title":"Redox Biol"},{"key":"R44-20260122","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.biopha.2018.05.130","article-title":"Simvastatin ameliorates diabetic nephropathy by attenuating oxidative stress and apoptosis in a rat model of streptozotocin-induced type 1 diabetes","volume":"105","author":"Al-Rasheed","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"R45-20260122","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.jsxm.2020.04.390","article-title":"Baicalein alleviates erectile dysfunction associated with streptozotocin-induced type I diabetes by ameliorating endothelial nitric oxide synthase dysfunction, inhibiting oxidative stress and fibrosis","volume":"17","author":"Chen","year":"2020","journal-title":"J Sex Med"},{"key":"R46-20260122","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.jsxm.2018.07.013","article-title":"Rapamycin supplementation may ameliorate erectile function in rats with streptozotocin-induced type 1 diabetes by inducing autophagy and inhibiting apoptosis, endothelial dysfunction, and corporal fibrosis","volume":"15","author":"Lin","year":"2018","journal-title":"J Sex Med"},{"key":"R47-20260122","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/1753-0407.12181","article-title":"Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction","volume":"7","author":"Castela","year":"2015","journal-title":"J Diabetes"},{"key":"R48-20260122","doi-asserted-by":"crossref","first-page":"764641","DOI":"10.1155\/2015\/764641","article-title":"Fibrosis related inflammatory mediators:role of the IL-10 cytokine family","volume":"2015","author":"Sziksz","year":"2015","journal-title":"Mediators Inflamm"},{"key":"R49-20260122","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1111\/jsm.12477","article-title":"Nebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum and penile arteries from diabetic patients by enhancing the NO\/cGMP pathway","volume":"11","author":"Mart\u00ednez-Salamanca","year":"2014","journal-title":"J Sex Med"},{"key":"R50-20260122","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/j.1743-6109.2009.01587.x","article-title":"Diabetes exacerbates the functional deficiency of NO\/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries","volume":"7","author":"Angulo","year":"2010","journal-title":"J Sex Med"},{"key":"R51-20260122","doi-asserted-by":"crossref","first-page":"11870","DOI":"10.1073\/pnas.0502488102","article-title":"Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction","volume":"102","author":"Musicki","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R52-20260122","doi-asserted-by":"crossref","first-page":"6834236","DOI":"10.1155\/2020\/6834236","article-title":"Human tissue kallikrein 1 improves erectile dysfunction of streptozotocin-induced diabetic rats by inhibition of excessive oxidative stress and activation of the PI3K\/AKT\/eNOS pathway","volume":"2020","author":"Luan","year":"2020","journal-title":"Oxid Med Cell Longev"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:28:08Z","timestamp":1786724888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aja202528","relation":{},"ISSN":["1745-7262","1008-682X"],"issn-type":[{"value":"1745-7262","type":"print"},{"value":"1008-682X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,5]]},"assertion":[{"value":"2024-12-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-20","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}