Endometriosis Treatment: Role of Natural Polyphenols as Anti-Inflammatory Agents

Abstract

Endometriosis is an estrogen-dependent common chronic inflammatory disease defined by the presence of extrauterine endometrial tissue that promotes pelvic pain and fertility impairment. Its etiology is complex and multifactorial, and several not completely understood theories have been proposed to describe its pathogenesis. Indeed, this disease affects women's quality of life and their reproductive system. Conventional therapies for endometriosis treatment primarily focus on surgical resection, lowering systemic levels of estrogen, and treatment with non-steroidal anti-inflammatory drugs to counteract the inflammatory response. However, although these strategies have shown to be effective, they also show considerable side effects. Therefore, there is a growing interest in the use of herbal medicine for the treatment of endometriosis; however, to date, only very limited literature is present on this topic. Polyphenols display important anti-endometriotic properties; in particular, they are potent phytoestrogens that in parallel modulates estrogen activity and exerts anti-inflammatory activity. The aim of this review is to provide an overview on anti-inflammatory activity of polyphenols in the treatment of endometriosis.

Keywords: NSAIDs; anti-inflammatory activity; endometrium; polyphenols.

Figure 1

ASRM classification of endometriosis I–IV stages. Pink arrows indicate superficial implants; purple arrows indicate dense adhesions; blue arrows indicate filmy adhesions. Created with biorender.com.

Figure 2

Flow chart meta-analyses (PRISMA).

Figure 3

Molecular and inflammatory mechanisms driving EMS. The figure depicts the main alterations occurring in EMS. In particular, increased levels of CYP19A1 and StAR enzymes, together with reduced HSD17β2, boost E2 production. Concomitantly, ERβ over-expression triggers COXs expression/activation and PG increase. Resistance to P4, which normally elevates RA levels, hinders HSD17β2 expression in epithelial cells, thus contributing to enhancing E2 levels. Moreover, the rise in ER/ERβ ratio also promotes inflammation by enhancing cytokine expression (IL-1β, IL-8, IL-6, TNFα) and further stimulating COX-2 activity. This latter process metabolizes AA to produce PGE₂. Inflammation drives NF-κB pathway activation, thus promoting macrophage recruitment. Created with biorender.com.

Figure 4

Structure of quercetin (a) and quercetin-4′-O-β-d-glucoside (b).

Figure 5

Structure of luteolin.

Figure 6

Structure of genistein.

Figure 7

Structure of cis-resveratrol (a) and trans-resveratrol (b).