<i>Astragalus</i><i> membranaceus</i> Fisch. ex Bunge-derived astragaloside IV recovers bilateral cavernous nerve injury-induced erectile dysfunction and corporal fibrosis by inhibiting the TGF-β1/Smad2 pathway in rats


Sevgi S., Cavusoglu Nalbantoglu İ., Kerimoglu G., Kesim S. M., Burnett A. L., Sezen S. F.

JOURNAL OF ETHNOPHARMACOLOGY, cilt.355, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 355
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.jep.2025.120640
  • Dergi Adı: JOURNAL OF ETHNOPHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, International Bibliography of Social Sciences, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, CINAHL, Index Islamicus, International Pharmaceutical Abstracts, Veterinary Science Database
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

Ethnopharmacological relevance Astragalus membranaceus Fisch. ex Bunge, a medicinal herb widely used in Traditional Chinese Medicine, contains Astragaloside IV (AS-IV) as its active component which has shown diverse pharmacological activities like antifibrotic effect in a number of preclinical studies. Given the lack of effective therapies for erectile dysfunction (ED) associated with nerve injury-induced cavernous fibrosis, AS-IV has emerged as a promising candidate for targeting fibrosis-related pathologies. Aim of the study This study aimed to investigate the potential protective effect of AS-IV mediated by TGF-beta 1/Smad2 signal inhibition, on ED in a rat model of bilateral cavernous nerve injury (BCNI). Materials and methods Seventy-two male Sprague-Dawley rats were divided equally into six experimental groups (n = 6) in each of the 7 and 14 days post-injury: Sham + vehicle, Sham+1 mg/kg/day AS-IV, Sham+5 mg/kg/day AS-IV, BCNI + vehicle, BCNI+1 mg/kg/day AS-IV and BCNI+5 mg/kg/day AS-IV. Erectile function was evaluated by intracavernous pressure (ICP)/mean arterial pressure (MAP) ratios. Furthermore, penile tissues were analyzed by western blotting (TGF-beta 1, p-Smad2, Smad2, fibronectin protein expressions) and Masson's trichrome staining (smooth muscle content and collagen deposition). Results Erectile function (maximum ICP/MAP and total ICP/MAP) was significantly reduced in BCNI groups at both post-injury (p < 0.001). 7 days treatment of AS-IV showed no effect, whereas both low and high doses for 14 days significantly preserved erectile function (p < 0.01). In the BCNI groups at both 7 and 14 days post-injury, TGF-beta 1 and fibronectin expression, as well as the p-Smad2/Smad2 ratio, were significantly increased (p < 0.05). AS-IV dose-dependently suppressed the elevations in p-Smad2/Smad2 ratio, TGF-beta 1 and fibronectin expressions at both post-injuries. Fibrotic changes were markedly aggravated in BCNI group at 14 days post-injury (p < 0.05). Corporal fibrosis was histologically prevented after only 14 days of high-dose AS-IV treatment. (p < 0.01). Conclusions AS-IV ameliorated BCNI-induced ED in rats by reducing corporal fibrosis via the inhibition of the TGF-beta 1/Smad2 pathway. These preliminary findings suggest the need for further investigation into its therapeutic potential for nerve injury-induced ED.