Quercetin and its effects on endometriosis

Quercetin modulates signaling pathways to enhance decidualization in endometriosis, study finds

Key Points

Highlight

• Investigation of quercetin’s impact on endometrial stromal cells revealed enhanced decidualization and potential pathways offering new therapeutic insights for endometriosis management.

Importance

• Quercetin, a natural compound found in certain foods, could be a helpful treatment for endometriosis.
• Further understanding of its mechanisms could pave the way for novel treatment approaches targeting the root causes of this complex disorder.

What's done here 

• The effects of quercetin on the decidualization process were evaluated and compared between patients with endometriosis and controls using menstrual-effluent derived endometrial stromal cells (ME-eSCs).
• Different signaling pathways, oxidative stress, senescence markers, and apoptosis were examined.

Key results

• Quercetin significantly reduced ME-eSC proliferation, and enhanced decidualization, as indicated by increased IGFBP1 and PRL production.
• Endometriosis-eSCs exhibited impaired decidualization which quercetin effectively reversed.
• Quercetin did not induce intracellular cAMP production or exert antioxidant effects.
• It rapidly reduced the phosphorylation of AKT, ERK1/2, PRAS40, and WNK and increased phosphorylation of p53 and expression of total p53 protein.
• It reduced senescence-like phenotypes and induced apoptosis in a subset of cells.

Limitations

• Difficulty in identifying senescent cells due to tissue-specific markers.
• Quercetin's low bioavailability

Lay Summary

Endometriosis, as a disease characterized by chronic inflammation and fibrosis, could be a potential target for quercetin, a flavonoid found in various foods and botanicals, and a known senolytic agent with many effects including antioxidant, anti-inflammatory, and immune-modulatory properties. Studies suggest its potential efficacy in animal models and pain reduction in endometriosis patients.

Delenko et al. from New York, under the leadership of Dr. Gregersen and Dr Metz from Feinstein Institutes for Medical Research-Northwell Health, USA investigated the menstrual-effluent derived endometrial stromal cells (ME-eSCs) in patients with endometriosis, confirmed the defects in decidualization and altered differentiation of eSCs in these patients. Their new study preprinted in MedRXive, evaluated and compared the effects of quercetin on the decidualization process between patients with endometriosis and controls. After growing collected ME-eSCs from the patients and the controls, investigations were performed on signaling pathways, including AKT and p53, exploring quercetin's role in mitigating oxidative stress-induced impairment of decidualization, and assessing senescence markers and apoptosis. Various assays were conducted, including proliferation, immunofluorescent staining, gene expression analyses, and flow cytometry. 

Quercetin significantly reduced ME-eSC proliferation dose-dependently, inhibiting proliferation even in cells from endometriosis patients. Moreover, it enhanced decidualization, as indicated by increased IGFBP1 and PRL production, with the most notable effects observed with a 4-hour pre-treatment regimen. Endometriosis-eSCs exhibited impaired decidualization, which quercetin effectively reversed to levels comparable to healthy controls.

Quercetin did not induce intracellular cAMP production or exert antioxidant effects. However, it altered multiple signaling pathways by rapidly reducing the phosphorylation of AKT, ERK1/2, PRAS40, and WNK. It was also found that ERK1/2 and AKT pathways intersected to suppress p53. Quercetin also increased the phosphorylation of p53 and enhanced the expression of total p53 protein. Additionally, it reduced senescence-like phenotypes and induced apoptosis in a subset of cells.

 The authors add that even though quercetin shows promise in improving fecundity and reducing endometrial implant growth, its low bioavailability limits efficacy. Formulations like Quercetin Phytosome® aim to enhance solubility and bioavailability. They also discuss that identifying senescent cells remains challenging due to tissue-specific markers and future studies should focus on the non-invasive sampling methods when collecting the samples.

They conclude by saying that further investigation of senescence in endometriosis and exploring quercetin as a therapy or preventive measure is needed. Clinical trials assessing quercetin's efficacy in endometriosis prevention are warranted, potentially monitoring decidualization defects and senescent phenotypes in menstrual effluent.

Research Source: https://www.medrxiv.org/content/10.1101/2023.08.30.23294800v2