Unlocking the Potential: How Flavonoids Affect Angiogenesis, Oxidative Stress, Inflammation, Proliferation, Invasion, and Alter Receptor Interactions in Endometriosis

ABSTRACT Endometriosis, though not classified as a carcinogenic condition, shares features such as oxidative stress, migration, invasion, angiogenesis, and inflammation with tumor cells. This study aims to review the effects of flavonoids on these processes and their molecular mechanisms in preventing and treating endometriosis. A comprehensive review was conducted, involving a literature search in online databases using keywords like “endometriosis,” “endometrioma,” and “flavonoid.” Two authors screened the literature based on predefined criteria, and the selected studies were summarized in a structured data extraction table. Studies reviewed showed that various flavonoids impact key processes in endometriosis, including angiogenesis, inflammation, oxidative stress, and invasiveness. Flavonoids such as 2′,7'‐dichlorodihydrofluorescein diacetate (H2DCF‐DA), naringenin, apigenin, myricetin, 5,7‐dimethoxyflavone (DMF), chrysin, and 6,8‐diprenylorobol were found to induce oxidative stress. Xanthohumol, isoliquiritigenin, and luteolin demonstrated effects on angiogenesis. Apigenin, isoliquiritigenin, and luteolin exhibited anti‐inflammatory properties. Additionally, 3,6‐dihydroxyflavone, isoliquiritigenin, and naringenin displayed anti‐invasive activities. Flavonoid–receptor interactions further enhance their therapeutic potential in endometriosis management. Flavonoids such as nobiletin, chrysin, and daidzein modulate PPARγ and PPARα, reducing inflammation, promoting apoptosis, and improving lipid metabolism. These interactions regulate critical pathways in angiogenesis and immune responses. Additionally, flavonoids impact the aryl hydrocarbon receptor (AhR), with compounds like resveratrol inhibiting cell proliferation and cholesterol biosynthesis, further suppressing lesion growth. The ability of flavonoids like quercetin and kaempferol to antagonize NR4A1 leads to reduced cell proliferation and oxidative stress in endometriotic tissues. These findings offer insights into the mechanisms through which specific flavonoids modulate angiogenesis, inflammation, oxidative stress, and invasiveness in endometriosis. By targeting receptors such as PPARs, AhR, and NR4A1, flavonoids demonstrate the capacity to modulate both metabolic and inflammatory pathways, offering a multifaceted approach to managing endometriosis. Flavonoids can selectively target pathophysiologic molecules and pathways implicated in the condition. Consequently, leveraging the therapeutic attributes of flavonoids could lead to novel strategies for managing endometriosis.