Yu Jundong, Zhang Xue, Wang Jing, Cheng Kaixian, Yang Binrui, Du Jun, Chen Liang, Wu Yingchun, Li Yiming
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Nutrilite Health Institute, Amway (Shanghai) Innovation & Science Co., Ltd., Shanghai, 201203, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118756. doi: 10.1016/j.jep.2024.118756. Epub 2024 Sep 1.
Fructus Rubi (FR), a food material with medicinal value, is used in traditional Chinese medicine (TCM) for treatment of various kidney-related problems, such as impotence, spermatorrhea, and frequent urination. It is also frequently used to produce diverse functional foods in China.
The purpose of this research was to assess the therapeutic effects of FR diterpene glycosides on RWPE-1 epithelial cell (RWPE-1), a human normal prostatic epithelial cell, and benign prostate hyperplasia (BPH) rats, both of which had been exposed to dihydrotestosterone (DHT) and testosterone propionate (TP), respectively, and to investigate the mechanism of action.
Target proteins that could stably bind to certain diterpene glycosides were screened through drug affinity responsive target stability combined with mass spectrometry (DARTS/MS). DHT-induced RWPE-1 cells were used to detect drug activity. TP was subcutaneously injected to induce BPH in rats. The extract of diterpene glycosides from FR (FDS) was orally administered for 28 days. The DHT levels in the serum and prostate tissue of the rats were measured through enzyme-linked immunosorbent assay (ELISA), and to analyze cell proliferation and epithelial-mesenchymal transition (EMT), the protein expression of prostate-specific antigen (PSA), androgen receptor (AR), steroid 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen (PCNA), S100 calcium-binding protein A2 (S100A2), transforming growth factor-β1 (TGF-β1), E-cadherin, vimentin, and Smad4 was determined through western blotting (WB), immunohistochemistry (IHC), or immunofluorescence (IF).
FDS reduced the proliferation of DHT-induced RWPE-1 cells. It also significantly inhibited rat prostate enlargement; decreased DHT levels in the serum and prostate tissue; inhibited the protein expression of AR, PSA, PCNA, S100A2, TGF-β1, E-cadherin, and Smad4; and increased the protein expression of E-cadherin.
The present study is the first to report that diterpene glycosides isolated from FR inhibited BPH at the cellular level, regulated the proliferation of prostate cells through the androgen signaling pathway, and prevented EMT in the prostate through the S100A2-mediated TGF-β/Smad signaling pathway. These results indicate that FDS is a promising multitarget therapy for BPH.
覆盆子是一种具有药用价值的食物原料，在传统中药中用于治疗各种与肾脏相关的问题，如阳痿、遗精和尿频。在中国，它也经常被用于生产各种功能性食品。
本研究的目的是评估覆盆子二萜糖苷对人正常前列腺上皮细胞RWPE - 1和良性前列腺增生（BPH）大鼠的治疗效果，这两种细胞和大鼠分别已暴露于二氢睾酮（DHT）和丙酸睾酮（TP），并研究其作用机制。
通过药物亲和响应靶点稳定性结合质谱法（DARTS/MS）筛选能与某些二萜糖苷稳定结合的靶蛋白。使用DHT诱导的RWPE - 1细胞检测药物活性。皮下注射TP诱导大鼠BPH。口服覆盆子二萜糖苷提取物（FDS）28天。通过酶联免疫吸附测定（ELISA）测量大鼠血清和前列腺组织中的DHT水平，并通过蛋白质印迹法（WB）、免疫组织化学（IHC）或免疫荧光（IF）测定前列腺特异性抗原（PSA）、雄激素受体（AR）、2型类固醇5α - 还原酶（SRD5A2）、增殖细胞核抗原（PCNA）、S100钙结合蛋白A2（S100A2）、转化生长因子 - β1（TGF - β1）、E - 钙黏蛋白、波形蛋白和Smad4的蛋白表达，以分析细胞增殖和上皮 - 间质转化（EMT）。
FDS降低了DHT诱导的RWPE - 1细胞的增殖。它还显著抑制大鼠前列腺肿大；降低血清和前列腺组织中的DHT水平；抑制AR、PSA、PCNA、S100A2、TGF - β1、E - 钙黏蛋白和Smad4的蛋白表达；并增加E - 钙黏蛋白的蛋白表达。
本研究首次报道从覆盆子中分离出的二萜糖苷在细胞水平上抑制BPH，通过雄激素信号通路调节前列腺细胞的增殖，并通过S100A2介导的TGF - β/Smad信号通路预防前列腺中的EMT。这些结果表明FDS是一种有前景的用于治疗BPH的多靶点疗法。
