Li Xiang, Shi Guobing
College of life sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, China.
Pharmaceutical Department, Liaoning Cancer Hospital, Shenyang, China.
Ann Transl Med. 2021 Apr;9(8):666. doi: 10.21037/atm-21-656.
Ferulic acid (FA) and icariin (ICA), as the active compounds derived from and , respectively, have been shown to promote blood circulation, regulate menstruation, exhibit anti-inflammatory effects, and modulate estrogen levels. The aim of this study was to elucidate the possible mechanism of FA, ICA, and FA-ICA on estrogen-induced mammary gland hyperplasia (MGH) in rats.
Hematoxylin and eosin (HE) staining was performed to record the pathological changes in breast tissue, and enzyme-linked immunosorbent assay (ELISA) was utilized to determine the serum levels of luteinizing hormone (LH), PRL (prolactin), testosterone (T), estradiol (E2), follicular stimulating hormone (FSH), and progesterone (P). The message RNA (mRNA) expression levels of extracellular signal-regulated kinase 1 (ERK1), extracellular signal-regulated kinase 2 (ERK2), estrogen receptor (ER), and progesterone receptor (PR) were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. Furthermore, ER, phosphorylated-ER, PR, p-PR, ERK1/2, and p-ERK1/2 protein factors in the ERK signaling pathway were evaluated by Western blotting. Simultaneously, changes in breast height, diameter, body weight, and organ index were all recorded.
We found that FA and ICA could modulate the degree of breast swelling, and reduce the body weight, thymus index, and uterus index. Furthermore, it could also block the pathological changes of MGH, including the number of mammary lobules, and the proliferation or expansion of acini and ducts. Moreover, treatment with FA and ICA remarkably down-regulated the serum expression levels of LH, PRL, T, and E2, as well as the mRNA expression levels of ERα, PR, ERK1, and ERK2. Additionally, protein levels of ERα, p-ERα, PR, p-PR, ERK1/2, and p-ERK1/2 in breast tissue were down-regulated, however the serum content of FSH and P was up-regulated.
Our outcomes revealed that FA and ICA might potentially inhibit ERα, PR, ERK1/2, and their phosphorylated proteins via the ERK signaling pathway, thus indicating a positive feedback control for the degree of breast hyperplasia.
阿魏酸（FA）和淫羊藿苷（ICA）分别是从[具体来源1]和[具体来源2]中提取的活性化合物，已被证明具有促进血液循环、调节月经、抗炎以及调节雌激素水平的作用。本研究旨在阐明FA、ICA以及FA - ICA对雌激素诱导的大鼠乳腺增生（MGH）的可能作用机制。
采用苏木精-伊红（HE）染色记录乳腺组织的病理变化，利用酶联免疫吸附测定（ELISA）法测定血清中促黄体生成素（LH）、催乳素（PRL）、睾酮（T）、雌二醇（E2）、促卵泡生成素（FSH）和孕酮（P）的水平。通过实时逆转录-聚合酶链反应（RT-PCR）分析检测细胞外信号调节激酶1（ERK1）、细胞外信号调节激酶2（ERK2）、雌激素受体（ER）和孕酮受体（PR）的信使核糖核酸（mRNA）表达水平。此外，通过蛋白质印迹法评估ERK信号通路中的ER、磷酸化-ER、PR、p-PR、ERK1/2和p-ERK1/2蛋白因子。同时，记录乳房高度、直径、体重和器官指数的变化。
我们发现FA和ICA可以调节乳房肿胀程度，并降低体重、胸腺指数和子宫指数。此外，它还可以阻止MGH的病理变化，包括乳腺小叶数量以及腺泡和导管的增殖或扩张。此外，FA和ICA处理显著下调了血清中LH、PRL、T和E2的表达水平，以及ERα、PR、ERK1和ERK2的mRNA表达水平。此外，乳腺组织中ERα、p-ERα、PR、p-PR、ERK1/2和p-ERK1/2的蛋白水平下调，然而血清中FSH和P的含量上调。
我们的结果表明，FA和ICA可能通过ERK信号通路潜在地抑制ERα、PR、ERK1/2及其磷酸化蛋白，从而表明对乳腺增生程度存在正反馈控制。
