Intralesional baicalein attenuates fibrosis in a rat model of peyronie’s disease by inhibiting TGF-β1/smad signaling

Abstract

TGF-β1 plays a fundamental role in the pathogenesis of Peyronie’s disease, driving the excessive extracellular matrix accumulation and fibroblast activation characteristic of fibrosis. As in many fibrotic disorders, its action via Smad transcription factors presents a key therapeutic target. Given the notable deficiency in proven effective conservative treatments for Peyronie’s disease, particularly in its acute phase, this study aimed to investigate the efficacy of baicalein, a flavonoid known to inhibit the TGF-β1/Smad signaling pathway, thereby offering a promising therapeutic strategy. We established a rat model of Peyronie’s disease on 30 male Wistar albino rats using a single intratunical injection of a combined solution containing 0.1 mL recombinant TGF-β1 protein (0.01 μg/μL) and 0.1 mL sodium tetradecyl sulfate (0.01 μg/μL, 3%), and administered baicalein intralesionally at low (0.8 μg/L, 50 μL), moderate (1.6 μg/L, 50 μL), and high (3.2 μg/L, 50 μL) doses. There were no significant differences among the groups in terms of animal weights or degrees of curvature before and after treatment. Our comprehensive analysis of blindly performed histopathological and immunohistochemical parameters, including tunica albuginea thickness, fibrosis severity, and smooth muscle content, demonstrated that intralesional baicalein suppressed fibrosis formation in corporeal bodies (p = 0.002) in a dose-dependent manner, preserved crucial cavernosal smooth muscle tissue (p = 0.005), and effectively prevented pathological increases in tunica albuginea thickness (p = 0.002). Importantly, systemic toxicity was not detected in any of the subjects. As the first study to investigate intralesional baicalein for Peyronie’s disease, our findings positively contribute to the literature and underscore its potential as a safe, accessible, and highly effective agent. Further in vitro and in vivo research is warranted to fully explore baicalein’s capacity to address current treatment gaps in this challenging condition.