Therapeutic effects and mechanism of ferulic acid and icariin in mammary gland hyperplasia model rats via regulation of the ERK pathway

Abstract

Background: Ferulic acid (FA) and icariin (ICA), as the active compounds derived from Angelica sinensis and Epimedium brevicornum Maxim, 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.Methods: 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.Results: 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.Conclusions: 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.

Ferulic Acid: A Review of Pharmacology, Toxicology, and Therapeutic Effects on Pulmonary Diseases

“…Sustained activation of ERK can promote proliferation and migration of tumor cells. FA is capable of inhibiting the overexpression of p-ERK1/2 and ERK1/2 proteins, thus exerting a proliferation-inhibiting effect (Figure 2D) [127].…”

Epimedium for Osteoporosis Based on Western and Eastern Medicine: An Updated Systematic Review and Meta-Analysis

“…As far as phytoestrogens’ effect on bone metabolism is concerned, previous studies have illustrated that Epimedium exhibited a certain estrogen-like effect, and Icariin, the main effective component of Epimedium brevicornum Maxim, which is used as the chemical marker for standardization of the quality of Epimedium extracts based on Chinese Pharmacopeia, may promote the secretion of E2 by granulosa cells ( Li and Shi, 2021 ). According to the individual RCT, Epimedium as an adjuvant might improve E2 significantly in clinical practice, while the meta-analysis could not detect convincing results with significant between-group difference, which may be induced by the paucity of data on the E2 in the osteoporosis population treated with Epimedium.…”