Fibrosis is characterized by excessive accumulation of extracellular matrix, which is a key feature of uterine fibroids, one of the most common benign tumors of the uterus.
While a significant number of individuals with uterine fibroids do not experience any symptoms, approximately 25% face notable symptoms such as excessive uterine bleeding, pelvic discomfort, and infertility. No standard protocol for uterine fibroid disease management or prevention, are available, finding a safe nonsurgical therapy is crucial.
It was already demonstrated that inhibition of fibrotic processes may restrict fibroid growth. Previous studies demonstrated that Epigallocatechin gallate (EGCG), a green tea compound with powerful antioxidant properties, could be a promising drug for uterine fibroids. In particular, an early phase clinical trial showed that EGCG was effective in reducing fibroid size and its associated symptoms; however, its mechanism of action has not been completely elucidated.
In this research, recently published in Scientific Reports, authors from Johns Hopkins Medicine highlighted the effects of EGCG on key signalling pathways involved in fibroid cell fibrosis.
They utilized laboratory cultures of uterine fibroids obtained from living patients. Since uterine fibroid cells possess a substantial extracellular matrix, the researchers devised experiments to specifically investigate the impact of EGCG treatment on protein expression associated with it. In particular, they focused on examining the effects of EGCG on fibronectin, a matrix protein, cyclin D1, a protein involved a protein involved in cell cycle progression, and connective tissue growth factor (CTGF) protein. Cyclin D1 resulted increased in fibroid cells and was significantly reduced by EGCG treatment that significantly also reduced mRNA or protein levels of key fibrotic proteins, including CTGF (86% decrease), suggesting antifibrotic effects. A comparative study to evaluate the ability of EGCG to regulate fibrosis with synthetic inhibitors was conducted showing greater or equivalent efficacy in regulating expression of key fibrotic mediators.
These results provide insight into mechanisms behind the observed clinical efficacy of EGCG against uterine fibroids, indicating that EGCG exhibits anti-fibrotic effects in fibroid cells and targets multiple signaling pathways involved in fibroid growth, particularly those associated with the extracellular matrix.
These findings provide further validation for the ongoing FRIEND (Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural Compound in Green Tea) study, registered under ClinicalTrials.gov identifier NCT05364008. This study focuses on investigating the effects of EGCG in women with fibroids who are actively seeking pregnancy. While the results of this study show promising outcomes, researchers emphasize the necessity for additional research, and caution against individuals attempting to self-administer green tea supplements without proper guidance.
Future investigations on EGCG will encompass clinical trials involving large and diverse patient populations. These trials aim to determine the optimal dosage of EGCG supplementation, as well as potential side effects associated with its usage.
Credit: Arseniy Kapran, Unsplash
