Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney Walker Boulevard, Augusta, GA, 30912, USA.
Department of Urology, Augusta University, Augusta, USA.
Sci Rep. 2023 Aug 1;13(1):12427. doi: 10.1038/s41598-023-39511-w.
Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms affect a large percentage of the male population and places a substantial burden on the world health system. Current therapies include 5-alpha reductase inhibitors and alpha-blockers that are only partially effective and pose a huge economic burden, emphasizing the urgent need for effective, economical therapies. We isolated nanovesicles from pomegranate juice (Punica Granatum) (referred to as 'POM-NVs') and report to our knowledge for the first time, that these vesicles possess therapeutic potential against BPH. Following extensive characterization of POM-NVs, we tested their therapeutic potential in vitro using BPH1 cell line and identified a potential anti-proliferative and pro-apoptotic effect. We further tested these vesicles using a clinically relevant xenograft mouse BPH model derived from human BPH tissues. Remarkably, POM-NVs could reverse the BPH phenotype conferred by TGF-β mediated signaling and induced epithelial-to-mesenchymal (EMT) reversal, leading to the restoration of prostate epithelial states in vivo and in vitro. Furthermore, these vesicles attenuated bone morphogenic protein 5 (BMP5) signaling, a cardinal alteration that is instrumental in driving BPH. Considering the large incidences of BPH and its associated economic burdens, our study has important implications and can potentially improve the clinical management of BPH.
良性前列腺增生（BPH）及相关下尿路症状影响了很大比例的男性人群，并给世界卫生系统带来了巨大负担。目前的治疗方法包括 5-α 还原酶抑制剂和 α-受体阻滞剂，这些方法仅部分有效，并带来巨大的经济负担，这强调了迫切需要有效的、经济的治疗方法。我们从石榴汁（Punica Granatum）中分离出纳米囊泡（简称“POM-NVs”），据我们所知，这是首次报道这些囊泡具有治疗 BPH 的潜力。在对 POM-NVs 进行广泛表征后，我们在体外使用 BPH1 细胞系测试了它们的治疗潜力，并确定了它们具有潜在的抗增殖和促凋亡作用。我们进一步使用源自人 BPH 组织的临床相关异种移植小鼠 BPH 模型测试了这些囊泡。值得注意的是，POM-NVs 可以逆转 TGF-β 介导的信号转导引起的 BPH 表型，并诱导上皮-间充质（EMT）逆转，从而在体内和体外恢复前列腺上皮状态。此外，这些囊泡还减弱了骨形态发生蛋白 5（BMP5）信号转导，这一改变对于推动 BPH 的发生至关重要。鉴于 BPH 的高发病率及其相关的经济负担，我们的研究具有重要意义，并可能改善 BPH 的临床管理。
