Therapeutic Approaches of Resveratrol on Endometriosis via Anti-Inflammatory and Anti-Angiogenic Pathways

Abstract

Endometriosis represents a severe gynecological pathology, defined by implantation of endometrial glands and stroma outside the uterine cavity. This pathology affects almost 15% of women during reproductive age and has a wide range of consequences. In affected women, infertility has a 30% rate of prevalence and endometriosis implants increase the risk of ovarian cancer. Despite long periods of studies and investigations, the etiology and pathogenesis of this disease still remain not fully understood. Initially, endometriosis was related to retrograde menstruation, but new theories have been launched, suggesting that chronic inflammation can influence the development of endometriosis because inflammatory mediators have been identified elevated in patients with endometriosis, specifically in the peritoneal fluid. The importance of dietary phytochemicals and their effect on different inflammatory diseases have been highlighted, and nowadays more and more studies are focused on the analysis of nutraceuticals. Resveratrol is a phytoestrogen, a natural polyphenolic compound with antiproliferative and anti-inflammatory actions, found in many dietary sources such as grapes, wine, peanuts, soy, berries, and stilbenes. Resveratrol possesses a significant anti-inflammatory effect via inhibition of prostaglandin synthesis and it has been proved that resveratrol can exhibit apoptosis-inducing activities. From the studies reviewed in this paper, it is clear that the anti-inflammatory effect of this natural compound can contribute to the prevention of endometriosis, this phenolic compound now being considered a new innovative drug in the prevention and treatment of this disease.

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis

“…Resveratrol, a polyphenolic compound with anti-proliferative and anti-inflammatory actions, found in many dietary sources, is an alternative for endometriosis treatment (164). In a rat model with experimentally induced endometrial implant, resveratrol significantly reduced implant areas, while it decreased serum and peritoneal levels of VEGF and MCP-1.…”

The Role of Resveratrol in Mammalian Reproduction

“…Despite numerous studies, it is still debated whether resveratrol can be used alone or in combination with other estrogenic substances to regulate the reproductive function of animals or be used in estrogen replacement therapy of women [ 13 , 14 ]. With this aim, many authors have investigated the mechanism of action of resveratrol in different target organs in vitro [ 16 , 17 ] and in vivo [ 18 ].…”

“…Excellent and exhaustive reviews on the role of resveratrol on pregnancy [ 11 ], on the ovarian and endometrial function [ 12 , 13 , 14 ], and on the androgenic production of Leydig cells [ 15 ] have been published. This review aims to summarize the available data on the possible role of resveratrol on reproduction, with a particular focus on animals of veterinary interest.…”

Endometriosis Associated Infertility: A Critical Review and Analysis on Etiopathogenesis and Therapeutic Approaches

“…Elagolix, an oral anti-gonadotrophic agent is a novel and promising therapeutic method for endometriosis, that seems to stop the evolution of the disease and significantly reduce pain [ 196 ]. Resveratrol is a natural compound that possesses anti-angiogenic, anti-carcinogenic, proapoptotic, anti-oxidative, and anti-inflammatory effects and might provide novel therapeutic perspectives in endometriosis treatment [ 197 ]. Studies suggested that antioxidants such as melatonin, vitamins E and C may also be helpful to current endometriosis therapies [ 198 ].…”