环（Ser-Tyr）L/D空间异构对良性前列腺增生施加相反的作用
Cyclo(Ser-Tyr) L/D spatial isomerism exerts opposing effects on benign prostatic hyperplasia.
摘要(中文译文)
为探究两种异构体环（L-丝氨酸-L-酪氨酸）和环（D-丝氨酸-L-酪氨酸）在良性前列腺增生中的作用，并通过体外和体内实验阐明其作用机制。采用丙酸睾酮诱导良性前列腺增生（BPH）模型，评价环（L-Ser-L-Tyr）和环（D-Ser-L-Tyr）的药理作用。通过测量前列腺重量、计算前列腺指数，并进行组织病理学和生化分析来评估疗效和安全性。机制研究结合了转录组学、免疫组织化学、CCK-8实验、siRNA转染、Western blotting、分子对接和分子动力学模拟。环（L-Ser-L-Tyr）降低前列腺指数，减轻前列腺上皮增生和间质纤维化，降低TNF-α和IL-1β水平，并抑制炎症。相比之下，非那雄胺未能减轻前列腺纤维化，而环（D-Ser-L-Tyr）无治疗效果，且显著升高血清ALT和AST，提示潜在肝毒性。转录组分析显示，环（L-Ser-L-Tyr）逆转了BPH相关基因的升高表达，并影响癌症、凋亡、p53和MAPK信号等通路。在前列腺组织和细胞中，环（L-Ser-L-Tyr）降低AR和BCL-2的蛋白水平。在BPH-1细胞中，AR敲除显著降低BCL-2表达。分子动力学模拟显示，环（L-Ser-L-Tyr）与AR形成稳定复合物。环（L-Ser-L-Tyr）通过调节AR/BCL-2轴和炎症介质改善BPH，而环（D-Ser-L-Tyr）无效且可能具有肝毒性。这些结果支持环（L-Ser-L-Tyr）的临床潜力。
Abstract
To investigate the role of two isomers Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) in benign prostatic hyperplasia. Additionally, it seeks to elucidate their mechanisms of action through both in vitro and in vivo experiments. Benign prostatic hyperplasia (BPH) was induced using testosterone propionate. The pharmacological effects of Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) were evaluated. Efficacy and safety were assessed by measuring prostate weight, calculating the prostate index, and conducting histopathological and biochemical analyses. Mechanistic studies incorporated transcriptomics, immunohistochemistry, CCK-8 assays, siRNAs transfection, Western blotting, molecular docking, and molecular dynamics simulations. Cyclo (L-Ser-L-Tyr) reduced prostate index, attenuated prostatic epithelial hyperplasia and interstitial fibrosis, lowered TNF-α and IL-1β levels, and suppressed inflammation. In contrast, finasteride fails to alleviate prostate fibrosis, while Cyclo (D-Ser-L-Tyr) showed no therapeutic effect and significantly increased serum ALT and AST, indicating potential hepatotoxicity. Transcriptomic analysis showed that Cyclo (L-Ser-L-Tyr) reversed elevated expression of BPH-associated genes and affected pathways including cancer, apoptosis, p53, and MAPK signaling. In prostate tissues and cells, Cyclo (L-Ser-L-Tyr) reduced protein levels of AR and BCL-2. In BPH-1 cells, AR knockout markedly decreased BCL-2 expression. Molecular dynamics simulations showed that Cyclo (L-Ser-L-Tyr) forms a stable complex with AR. Cyclo (L-Ser-L-Tyr) ameliorates BPH by modulating the AR/BCL-2 axis and inflammatory mediators, whereas Cyclo (D-Ser-L-Tyr) is ineffective and may be hepatotoxic. These results support the clinical potential of Cyclo (L-Ser-L-Tyr).
如何引用
AMA
Liu Xun, Tan Rulan, Wang Tianyan, Geng Wenting, Shao Caiyun, Song Qiqi. Cyclo(Ser-Tyr) L/D spatial isomerism exerts opposing effects on benign prostatic hyperplasia.. Biochemical and biophysical research communications. 2026; doi:10.1016/j.bbrc.2026.154125.
APA
Liu Xun, Tan Rulan, Wang Tianyan, Geng Wenting, Shao Caiyun, Song Qiqi (2026). Cyclo(Ser-Tyr) L/D spatial isomerism exerts opposing effects on benign prostatic hyperplasia.. Biochemical and biophysical research communications. https://doi.org/10.1016/j.bbrc.2026.154125
GB/T 7714
Liu Xun, Tan Rulan, Wang Tianyan, Geng Wenting, Shao Caiyun, Song Qiqi. Cyclo(Ser-Tyr) L/D spatial isomerism exerts opposing effects on benign prostatic hyperplasia.[J]. Biochemical and biophysical research communications, 2026 doi:10.1016/j.bbrc.2026.154125.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出