Polyphenols as a Diet Therapy Concept for Endometriosis-Current Opinion and Future Perspectives

Abstract

Endometriosis represents an often painful, estrogen-dependent gynecological disorder, defined by the existence of endometrial glands and stroma exterior to the uterine cavity. The disease provides a wide range of symptoms and affects women's quality of life and reproductive functions. Despite research efforts and extensive investigations, this disease's pathogenesis and molecular basis remain unclear. Conventional endometriosis treatment implies surgical resection, hormonal therapies, and treatment with nonsteroidal anti-inflammatory drugs, but their efficacy is currently limited due to many side effects. Therefore, exploring complementary and alternative therapy strategies, minimizing the current treatments' adverse effects, is needed. Plants are sources of bioactive compounds that demonstrate broad-spectrum health-promoting effects and interact with molecular targets associated with endometriosis, such as cell proliferation, apoptosis, invasiveness, inflammation, oxidative stress, and angiogenesis. Anti-endometriotic properties are exhibited mainly by polyphenols, which can exert a potent phytoestrogen effect, modulating estrogen activity. The available evidence derived from preclinical research and several clinical studies indicates that natural biologically active compounds represent promising candidates for developing novel strategies in endometriosis management. The purpose of this review is to provide a comprehensive overview of polyphenols and their properties valuable for natural treatment strategy by interacting with different cellular and molecular targets involved in endometriosis progression.

Keywords: angiogenesis; apoptosis; diet therapy; endometriosis; inflammation; invasion; molecular targets; oxidative stress; polyphenols.

Figure 1

Schematic representation of dysregulated physiological processes in the endometriotic lesion. Endometriotic lesions consist of epithelial and stromal endometrial cells originating form retrograde menstruation. The endometrial cells subsequently attach to the underlying peritoneal mesothelium, proliferate, and initiate pro-endometriotic microenvironment formation. Cell proliferation and resistance to apoptosis, cell adhesion, inflammation, oxidative stress, and hormone signaling are augmented by the interactions of multiple cells and secretion of cytokines, chemokines, and hormones, which facilitate endometriotic lesion progression. This figure was made using graphic components obtained from the website: www.servier.com/powerpoint-imagebank (15 March 2021). Abbreviations used in graphics: 17β-HSD type 2, 17β-hydroxysteroid dehydrogenase type 2; BAX, BCL-2 associated X protein; BCL-XL, B-cell lymphoma-extra large; BCL-2, B-cell lymphoma 2; COX-2, cyclooxygenase-2; eNOS, endothelial nitric oxide synthase; ERα, estrogen receptor alpha; ERβ, estrogen receptor beta; E2, estradiol; FAS, tumor necrosis factor receptor superfamily member 6; FASL tumor necrosis factor ligand superfamily member; FGFs, fibroblast growth factors; GPX, glutathione peroxidase; HGF, hepatocyte growth factor; HIF-1α, hypoxia-inducible-factor 1-alpha; IL-1β, interleukin 1β, IL-6, interleukin 6; IL-8, interleukin 8; iNOS, inducible nitric oxide synthase; MCP-1, monocyte chemoattractant protein 1; NF-κB, nuclear factor kappa B; NO, nitric oxide; PGE₂, prostaglandin E₂; PR-B, progesterone receptor isoform B; P4, progesterone; ROS, reactive oxygen species; RNS, reactive nitrogen species; SDF-1, stromal-cell-derived-factor 1; StAR, steroidogenic acute regulatory protein; SOD, superoxide dismutase; TGF-α, transforming growth factor alpha; TGF-β, transforming growth factor beta; TIMP-1, tissue inhibitor of metalloproteinase-1; VEGF, vascular endothelial growth factor.