Department of Pharmacology, College of Korean Medicine, Sang-ji University, Wonju-si, Gangwon-do, 26339, Korea.
AmcoBio Inc., 1789 Nambusunhwan-ro, Gwanak-gu, Seoul 08758, Korea.
Int J Mol Sci. 2020 Dec 15;21(24):9567. doi: 10.3390/ijms21249567.
, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized on prostatic cells. We standardized 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.
，广泛应用于传统中药，具有抗勃起功能障碍和多尿的药理作用，这些都是良性前列腺增生（BPH）的病理症状。虽然有传统用途和对 BPH 的研究，但据我们所知，没有研究调查标准化对前列腺细胞的增殖抑制作用的确切分子机制。我们对 30%乙醇提取物（COFE）进行了标准化，并证明了 COFE 对人 BPH 上皮细胞和睾酮诱导的大鼠 BPH 的治疗作用。体外研究使用 BPH-1 细胞表明，BPH 相关和 E2F 转录因子 1（E2F1）依赖性细胞周期标志物上调，而 COFE 治疗明显抑制 BPH 上皮细胞的增殖，并减少 G1 和 S 检查点基因的过度表达。此外，COFE 给药可缓解雄激素依赖性前列腺增大在睾酮诱导的 BPH 动物模型中。COFE 通过抑制抗凋亡标志物、抑制 PCNA 表达以及调节 BPH 大鼠中 E2F1/pRB 依赖性细胞周期标志物发挥这些抗 BPH 作用。这些结果表明，COFE 通过调节 PCNA/E2F1 依赖性细胞周期信号通路发挥增殖抑制作用，无论是在体内还是体外。这些发现揭示了 COFE 的治疗潜力，可作为 BPH 治疗的替代品。
