Song Hye-Yeong, Choi Jinsu, Jeong Eunwoo, Park Harang, Moon Juyeong, Kim Min-Ah, Rustamov Javokhir, Yoo Hwan-Soo, Kim Tack-Joong
Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea.
College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea.
Biomedicines. 2025 Sep 4;13(9):2151. doi: 10.3390/biomedicines13092151.
: Estrogen deficiency-related menopause is associated with various physical and psychological symptoms. Although hormone replacement therapy (HRT) effectively alleviates these symptoms, its long-term use is associated with several side effects such as an increased risk of breast cancer and cardiovascular disease. Consequently, there is a growing interest in some plant-derived phytoestrogens that are considered safer alternatives to estrogen. Recent studies on confirmed their anti-inflammatory and antioxidant properties; however, their effects on menopausal health remain unclear. Therefore, the aim of this study was to investigate the estrogen-like effects of root (SB-R) extract, a potential phytoestrogen. : Briefly, the MCF-7 cell line, a widely used in vitro model for assessing estrogen-like activity, was treated with SB-R extract and 17β-estradiol (E2; positive control) in the presence or absence of ICI 182,780 (Fulvestrant), an estrogen receptor antagonist. An E-screen assay and flow cytometry were performed to assess the effects of the treatments on cell proliferation and the cell cycle, respectively. Additionally, Western blotting and immunofluorescence assays were performed to elucidate the potential mechanisms underlying the estrogen-like effects of SB-R. : Treatment with SB-R extract promoted MCF-7 cell proliferation in a manner similar to E2. However, ICI 182,780 co-treatment inhibited the SB-R extract-induced increase in MCF-7 cell proliferation. Additionally, SB-R extract promoted cell cycle progression by increasing the proportion of cells in the S and G2/M phases. Moreover, Western blotting and immunofluorescence assays showed that SB-R extract increased the expression of estrogen receptor alpha (ERα). Furthermore, SB-R treatment activated downstream signaling pathways by enhancing AKT and ERK phosphorylation and upregulated the expression of cell cycle regulators, including cyclin D1, cyclin dependent kinase 4 (CDK4), cyclin E1, and cyclin dependent kinase 2 (CDK2). : SB-R exhibits estrogen-like activity by activating ERα-mediated AKT and ERK pathways and thereby increasing the expression of proteins involved in cell cycle regulation. This makes it a promising phytoestrogen candidate and a safer alternative to conventional hormonal therapy for alleviating menopausal symptoms.
雌激素缺乏相关的更年期与各种身体和心理症状有关。尽管激素替代疗法（HRT）能有效缓解这些症状，但其长期使用会带来一些副作用，如乳腺癌和心血管疾病风险增加。因此，人们对一些植物源性植物雌激素的兴趣日益浓厚，它们被认为是雌激素更安全的替代品。近期对[未提及具体内容]的研究证实了其抗炎和抗氧化特性；然而，它们对更年期健康的影响仍不明确。因此，本研究的目的是探究一种潜在植物雌激素——[未提及具体植物名称]根提取物（SB - R）的雌激素样作用。简要来说，MCF - 7细胞系是一种广泛用于评估雌激素样活性的体外模型，在存在或不存在雌激素受体拮抗剂ICI 182,780（氟维司群）的情况下，用SB - R提取物和17β - 雌二醇（E2；阳性对照）处理该细胞系。分别进行E - 筛选试验和流式细胞术以评估处理对细胞增殖和细胞周期的影响。此外，进行蛋白质免疫印迹和免疫荧光试验以阐明SB - R雌激素样作用的潜在机制。用SB - R提取物处理以类似于E2的方式促进了MCF - 7细胞增殖。然而，ICI 182,780共同处理抑制了SB - R提取物诱导的MCF - 7细胞增殖增加。此外，SB - R提取物通过增加处于S期和G2/M期的细胞比例促进细胞周期进程。而且，蛋白质免疫印迹和免疫荧光试验表明SB - R提取物增加了雌激素受体α（ERα）的表达。此外，SB - R处理通过增强AKT和ERK磷酸化激活下游信号通路，并上调细胞周期调节因子的表达，包括细胞周期蛋白D1、细胞周期蛋白依赖性激酶4（CDK4）、细胞周期蛋白E1和细胞周期蛋白依赖性激酶2（CDK2）。SB - R通过激活ERα介导的AKT和ERK途径展现出雌激素样活性，从而增加参与细胞周期调节的蛋白质表达。这使其成为一种有前景的植物雌激素候选物，也是缓解更年期症状的传统激素疗法更安全的替代品。
