stilbenes and Endometriosis

Palmitoylethanolamide is reported to solve pain and neuroinflammation in different models of chronic and neurodegenerative diseases. Some concerns have been illustrated for cautiously interpreting the available literature on the topic. Specifically, there is a lack of evidence about palmitoylethanolamide and female chronic pelvic pain. Concerns will be best solved by randomized trials. The present study was aimed at finding the best responders to micronized palmitoylethanolamide in female patient with chronic pelvic pain, using the existing literature at individual patient level, to help further randomized trial planning.. After a systematic research, eligible studies (the ones enrolled female patients treated for chronic pelvic pain or for dyspareunia, dysuria, dyschezia, and dysmenorrhea with or without chronic pelvic pain) were assessed at individual patient data level. Conditional probabilities were calculated to assess variables conditioning the rates of good responders (pain score points more or equal to 3 reduction), poor responders (2 pain score reduction), and nonresponders at a three-month follow-up.. Only cases treated with palmitoylethanolamide comicronized with polydatin for a short period can be assessed. Good responders are more than 50%. In chronic pelvic pain, there is a 19.0% conditional probability to find good responders among patients with pain score at enrolment of 6 to 8 and of 6.8% to find poor responders among patients with a pain score at enrolment of 6 to 8. Painful disease does not matter on responders' rates.. Best responders to comicronized palmitoylethanolamide/polydatin are patients with pain score higher than 6 at enrolment, irrespective of other variables.

Topics: Amides; Chronic Pain; Dysmenorrhea; Endometriosis; Ethanolamines; Female; Glucosides; Humans; Palmitic Acids; Pelvic Pain; Stilbenes

The aim of this review is to investigate the oxidant/antioxidant status and its regulatory mechanisms in patients with endometriosis and to summarize the antioxidant therapy as an alternative to hormonal therapy for endometriosis. Each keyword alone or in combination was used to search from PubMed and Embase by applying the filters of the title and the publication years between January 2000 and March 2020. Endometriosis is a chronic inflammatory disease characterized by repeated episodes of hemorrhage. Methemoglobin in repeated hemorrhage produces large amounts of superoxide anion via the autoxidation of hemoglobin. Excessive free-radical production causes redox imbalance, leading to inadequate antioxidant defenses and damage to endometrial cells, but may contribute to endometrial cell growth and survival through activation of various signaling pathways. In addition, to overcome excessive oxidative stress, estradiol participates in the induction of antioxidants such as superoxide dismutase in mitochondria. Several antioxidants that suppress free radicals may be effective in endometriosis-related pain. We searched for 23 compounds and natural substances that could reduce the pain caused by superoxide/reactive oxygen species in basic research and animal models. Next, we built a list of 16 drugs that were suggested to be effective against endometriosis other than hormone therapy in preclinical studies and clinical trials. Of the 23 and 16 drugs, 4 overlapping drugs could be potential candidates for clinically reducing endometriosis-related pain caused by superoxide anion/reactive oxygen species. These drugs include polyphenols (resveratrol and polydatin), dopamine agonists (cabergoline), and statins (simvastatin). However, no randomized controlled trials have evaluated the efficacy of these drugs. In conclusion, this review summarizes the following 2 points: superoxide anion generation by methemoglobin is enhanced in endometriosis, resulting in redox imbalance; and some compounds and natural substances that can suppress free radicals may be effective in endometriosis-related pain. Further randomized clinical trials based on larger series are mandatory to confirm the promising role of antioxidants in the nonhormonal management of endometriosis.

Topics: Animals; Antioxidants; Cabergoline; Dopamine Agonists; Endometriosis; Female; Glucosides; Humans; Methemoglobin; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Resveratrol; Signal Transduction; Simvastatin; Stilbenes; Superoxides

Endometriosis is characterized by the existence of endometrial tissue and stroma exterior to the uterus. Despite the high prevalence, the etiology of endometriosis remains elusive. The search for the most promising compounds for treatment of endometriosis has led to the identification of resveratrol. Resveratrol, a plant-derived polyphenolic phytoalexin, demonstrates broad-spectrum health beneficial effects, including anti-proliferative, anti-inflammatory, antineoplastic and antioxidant. Because of these properties and its wide distribution in plants, resveratrol is proposed as a great potential to treat endometriosis. In animal models of endometriosis, resveratrol supplementation has displayed beneficial results as it decreased the number and volume of endometrial implants, suppressed proliferation, vascularization, inflammation, cell survival and increased apoptosis. On the other hand, resveratrol treatment in-vitro studies, reduced invasiveness of endometriotic stromal cells (ESCs) and suppressed their inflammatory responses. In this review, we will summarize the recent studies in in-vitro and animal studies on resveratrol and endometriosis.

Topics: Animals; Biological Availability; Endometriosis; Female; Humans; Inflammation; Oxidative Stress; Resveratrol; Stilbenes

Aim of the study was to evaluate the effectiveness of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis.. Twenty-four patients with suspected endometriosis affected by severe pelvic pain were enrolled. All patients received two tablets a day of PEA 400 mg and 40 mg polydatin for 90 days consecutively. A Visual Analogic Scale was used for the assessment of the severity of global pain, dysmenorrhea, dyspareunia, dysuria and dischezia. A second questionnaire was submitted to patients to assess the quality of life. The compilation of a diary lead us to evaluate the monthly assumption of any painkillers. Patients were evaluated at the begin of the treatment and then monthly until the end of the study (90 days). The statistical analysis was performed by using the ANOVA for the analysis of variance.. Statistically significant results were found in relation to pelvic pain, dysmenorrhea and dyspareunia compared to the initial evaluation of patients. Results related to dysuria and dischezia were not statistically significant (P>0.05). The decrease in pelvic pain leads to an improvement of the quality of life of patients. A decreased assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) was also observed.. PEA could be considered an effective supplement to conventional analgesic therapies in the management of pelvic pain related to endometriosis.

Topics: Adult; Amides; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Drug Combinations; Dysmenorrhea; Dyspareunia; Endocannabinoids; Endometriosis; Ethanolamines; Female; Glucosides; Humans; Middle Aged; Palmitic Acids; Particle Size; Pelvic Pain; Pilot Projects; Quality of Life; Stilbenes; Surveys and Questionnaires; Young Adult

Aim of our study was to evaluate the effectiveness of the association between N-Palmitoylethanolamine and transpolydatin in the management of chronic pelvic pain related to EMS.. This was a randomized, double-blind, parallel-group, placebo-controlled clinical trial involving 61 subjects, submitted to a first line laparoscopic conservative surgery, who were randomized into 3 groups receiving: group A (n=21) the association N-Palmitoylethanolamine-transpolydatin 400 mg + 40 mg twice a day for 3 months; group B (n=20) the placebo for 3 months; group C (n=20) a single course of Celecoxib 200mg twice a day for 7 consecutive days. Assessments of the severity of pelvic endometriosis (pelvic pain, dysmenorrhoea and dyspareunia) were recorded before and after treatment on a questionnaire and a 10-point VAS. Differences between groups were verified with Kruskal-Wallis ANOVA for non-parametric multiple comparisons.. A marked decrease in dysmenorrhoea, dyspareunia and pelvic pain was observed in all groups, and the association between N-Palmitoylethanolamine and transpolydatin resulted to be more effective than placebo (P<.001). Additionally, the treatment with Celecoxib resulted in a decrease in pelvic pain more effective either than the association N-Palmitoylethanolamine and transpolydatin or placebo.. These preliminary results show that the association between micronized N-Palmitoylethanolamine and transpolydatin is effective in the management of pelvic pain related to endometriosis after laparoscopy. Additionally, this association seems to be safe, shows an optimal control of pain and can be used in patients who are unable to receive other therapies.

Topics: Adult; Amides; Analgesics; Double-Blind Method; Endocannabinoids; Endometriosis; Ethanolamines; Female; Glucosides; Humans; Laparoscopy; Palmitic Acids; Pelvic Pain; Phytotherapy; Pilot Projects; Stilbenes; Treatment Outcome; Young Adult

Staphylococcus aureus (S. aureus) causes severe inflammation in various infectious diseases, leading to high mortality. The clinical application of antibiotics has gained a significant curative effect. However, it has led to the emergence of various resistant bacteria. Therefore, in this study, we investigated the protective effect of polydatin (PD), a traditional Chinese medicine extract, on S. aureus lipoteichoic acid (LTA)-induced injury in vitro and in vivo. First, a significant improvement in the pathological conditions of PD in vivo was observed, suggesting that PD had a certain protective effect on LTA-induced injury in a mouse model. To further explore the underlying mechanisms of this protective effect of PD, LTA-induced murine macrophages were used in this study. The results have shown that PD could reduce the NF-κB p65, and IκBα phosphorylation levels increased by LTA, resulting in a decrease in the transcription of pro-inflammatory factors, such as TNF-α, IL-1β and IL-6. However, LTA can not only activate NF-κB through the recognition of TLR2 but also increase the level of intracellular reactive oxygen species (ROS), thereby activating NF-κB signalling. We also detected high levels of ROS that activate caspases 9 and 3 to induce apoptosis. In addition, using a specific NF-κB inhibitor that could attenuate apoptosis, namely NF-κB p65, acted as a pro-apoptotic transcription factor in LTA-induced murine macrophages. However, PD could inhibit the generation of ROS and NF-κB p65 activation, suggesting that PD suppressed LTA-induced injury by attenuating ROS generation and TLR2-NFκB signalling.

Topics: Animals; Antioxidants; Cell Survival; Endometriosis; Female; Gene Expression Regulation; Glucosides; I-kappa B Proteins; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Oxidative Stress; Protective Agents; RAW 264.7 Cells; Reactive Oxygen Species; Signal Transduction; Staphylococcus aureus; Stilbenes; Teichoic Acids; Toll-Like Receptor 2; Transcription Factor RelA; Uterus

Resistance to apoptosis, together with inflammatory and invasive activity, contributes to the pathogenesis of endometriosis; therefore, approaches that can safely enhance apoptosis in endometriotic tissue are highly sought after as a means of managing the disease. Although resveratrol (RVT) is known to induce apoptosis or increase sensitivity to apoptotic stimuli in various cancer cell types, its effect on human endometriosis has remained uncertain. This study aimed to investigate whether RVT induces or enhances apoptosis in human endometriotic stromal cells (ESCs).. Endometriotic tissues were collected, during laparoscopies, from women affected by ovarian endometriosis. ESCs were prepared, cultured, and treated with RVT. Apoptosis was assessed by annexin V-PI staining. Survivin mRNA expression in ESCs was examined using RT-PCR. ESCs were pre-treated with or without RVT and then incubated with TNF-α-related-apoptosis-inducing ligand (TRAIL), which is a known pro-apoptotic molecule.. RVT alone did not induce apoptosis in ESCs. RVT significantly reduced survivin mRNA expression (P < 0.05). Pre-treatment with RVT significantly enhanced TRAIL-induced apoptosis (8.13 ± 0.83% (control) versus 29.19 ± 7.39% (pre-treated with RVT), P < 0.05).. This study indicates that RVT suppresses survivin expression and enhances TRAIL-induced apoptosis in ESCs.

Topics: Apoptosis; Cells, Cultured; Endometriosis; Endometrium; Female; Humans; Inhibitor of Apoptosis Proteins; Resveratrol; Stilbenes; Stromal Cells; Survivin; TNF-Related Apoptosis-Inducing Ligand

The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p < 0.01) and decreased mean histopathological scores of the implants (p < 0.05), mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and MCP-1 (p = 0.01) levels after treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.

Topics: Angiogenesis Inhibitors; Animals; Ascitic Fluid; Disease Models, Animal; Endometriosis; Endometrium; Female; Inflammation; Leuprolide; Neovascularization, Pathologic; Rats; Rats, Wistar; Resveratrol; Stilbenes; Therapeutics

Resveratrol, a phytoalexin polyphenol, has anti-angiogenic, antioxidant, anti-inflammatory properties. We aimed to compare the anti-inflammatory and anti-angiogenic effects of resveratrol and leuprolide acetate (LA) in an experimental endometriosis model.. A prospective experimental study was conducted in a University Surgical Research Center. Thirty-three non-pregnant female Sprague-Dawley rats, in which experimental model of endometriosis were surgically induced were randomly divided into four groups. Group 1 was administered 30 mg/kg resveratrol i.m. for 14 days, group 2 was given 1mg/kg s.c. single dose LA, group 3 was administered both resveratrol and LA, and group 4 had no medication. After two weeks medication rats were sacrificed and size, histopathology and immunreactivity to matrix metalloproteinase (mmp)2, mmp9, vascular endothelial growth factor (VEGF) of the endometriotic implants were evaluated. Plasma and peritoneal fluid levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were analyzed.. The endometriotic implant volumes, histopathological grade and immunreactivity to mmp2, mmp9 and VEGF were significantly reduced (p<0.001), and plasma and peritoneal fluid levels of IL-6, IL-8 and TNF-α were significantly decreased in group 1 and group 2 in comparison to group 3 and group 4 (p < 0.001).. Resveratrol alone is a potential agent for the treatment of endometriosis and may be an alternative to LA. In contrast, the combination of LA and resveratrol decreased the anti-inflammatory and anti-angiogenic effects of each agent. Since resveratrol is widely used as an alternative therapy for a variety of conditions, it can undermine the effectiveness of LA. Therefore, caution should be exercised when used in combination with other agents.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Endometriosis; Endometrium; Female; Leuprolide; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Treatment Outcome; Vascular Endothelial Growth Factor A

Endometriosis is a chronic inflammatory disease. Sirtuin 1 (SIRT1) plays a role in regulation of inflammation. The role of SIRT1 in endometriosis remains unknown. We here addressed the anti-inflammatory effects of SIRT1 on endometriosis.. The expression of SIRT1 in human ovarian endometriomas and eutopic endometria were examined using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Endometriotic stromal cells (ESC) obtained from endometriomas were exposed to either resveratrol or sirtinol, an activator or inhibitor of sirtuins, respectively, and tumor necrosis factor (TNF)-α-induced interleukin (IL)-8 release from the ESC was assessed at mRNA and protein levels.. Both immunochemistry and RT-PCR demonstrated that SIRT1 was expressed in ESC and normal endometrial stromal cells. Resveratrol suppressed TNF-α-induced IL-8 release from the ESC in a dose-dependent manner while sirtinol increased IL-8 release.. These opposing effects of SIRT1-related agents suggest that IL-8 release from the ESC is modulated through the SIRT1 pathway. Resveratrol may have the potential to ameliorate local inflammation in endometriomas.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Benzamides; Cells, Cultured; Endometriosis; Endometrium; Enzyme Activators; Enzyme Inhibitors; Female; Humans; Interleukin-8; Naphthols; Ovarian Diseases; Ovary; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes; Stromal Cells

To test the adjuvant use of the combination of N-palmitoylethanolamine and transpolydatin in the medical treatment of endometriotic pain.. We enrolled 47 patients admitted to the Outpatient Endometriosis Care Unit of Ferrara University from January 2011 to December 2011. They were divided into two groups according to the endometriosis site (group A: recto-vaginal septum; group B: ovary). One tablet, containing 400 mg of micronized N-palmitoylethanolamine plus 40 mg transpolydatin, was administered twice daily on a full stomach for 90 days. Each patient was requested to grade the severity of dysmenorrhea, chronic pelvic pain, dyspareunia and dyschezia using a 0-10 cm visual analogic scale prior to beginning treatment (T0), after 30 days (T1), 60 days (T2) and 90 days (T3). The continuous and categorical variables were compared, respectively, using Student's t-test and the chi-square test. Analysis of variance for repeated measures was used to verify the reduction of endometriotic pain.. The intensity of endometriotic pain decreased significantly for both groups (p<0.0001). The efficacy of drug treatment was significant after 30 days. Pain intensity decreased equally in the two groups except for dysmenorrhea, which was reduced more rapidly in group B.. The combination of N-palmitoylethanolamine and transpolydatin reduced pain related to endometriosis irrespective of lesion site. It had a marked effect on chronic pelvic pain determined by deep endometriosis and on dysmenorrhea correlated to ovarian endometriosis.

Topics: Adult; Amides; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Contraceptives, Oral, Combined; Drug Combinations; Drug Therapy, Combination; Dysmenorrhea; Endocannabinoids; Endometriosis; Ethanolamines; Fascia; Female; Female Urogenital Diseases; Glucosides; Humans; Middle Aged; Ovarian Diseases; Pain Measurement; Palmitic Acids; Pelvic Pain; Prospective Studies; Stereoisomerism; Stilbenes; Young Adult

Does the phytochemical compound resveratrol inhibit vascularization of endometriotic lesions?. Resveratrol suppresses the development of new microvessels in endometriotic lesions by inhibiting endothelial cell proliferation.. Establishment and progression of endometriosis is crucially dependent on angiogenesis. Resveratrol is a pleiotropic agent, which dose-dependently suppresses the development of new blood vessels.. This was a randomized study in a mouse model of endometriosis. Twenty female BALB/c mice with surgically induced endometriosis were treated with resveratrol (40 mg/kg/day, n = 10) or vehicle (n = 10) for 4 weeks.. Peritoneal and mesenteric endometriotic lesions were surgically induced by uterine tissue transplantation into the abdominal cavity of BALB/c mice. The animals were daily treated with resveratrol (40 mg/kg) or vehicle by oral gavage. Lesion growth, vascularization, apoptosis and cell proliferation were subsequently analyzed by means of high-resolution ultrasound imaging, caliper measurements, histology and immunohistochemistry throughout an observation period of 4 weeks.. Resveratrol inhibited angiogenesis in peritoneal and mesenteric endometriotic lesions, as indicated by a significantly reduced microvessel density when compared with controls. Additional immunohistochemical analyses revealed that this was caused by a decreased proliferating activity of CD31-positive endothelial cells in the newly developing microvasculature of the lesions. In line with these findings, lesions in resveratrol-treated mice exhibited a reduced growth rate and a smaller final size than controls. This was associated with lower numbers of proliferating cell nuclear antigen- and Ki67-positive stromal and glandular cells. Apoptotic cells were not detectable in either group. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate controls. Statistical significance was accepted for a value of P < 0.05.. Endometriotic lesions were surgically induced by uterine tissue transplantation without the use of pathological endometriotic tissue of human origin. Therefore, the results obtained in this mouse model may not fully correlate to human patients with endometriosis.. Resveratrol is a potent inhibitor of vascularization in endometriotic lesions. This, most probably, causes the suppression of lesion growth. Accordingly, resveratrol represents a promising candidate therapy for future phytochemical treatment of endometriosis.. This work was supported by a grant of the 'Freunde des Universitätsklinikums des Saarlandes'. The authors have no conflicts of interest to declare.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Proliferation; Disease Models, Animal; Endometriosis; Endometrium; Female; Image Processing, Computer-Assisted; Immunohistochemistry; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Resveratrol; Stilbenes; Time Factors

To evaluate the effect of resveratrol on an experimentally induced endometriosis rat model.. After endometriotic implants were surgically formed, rats were randomly divided into 2 groups as control group (saline treated, n = 6) and resveratrol group (10 mg/kg/d, n = 6). The inflammatory markers and histopathological changes were assessed at the end of the treatment period. Results Our results showed (1) significant reduction in the implant size (P < .0005); (2) significantly decreased levels of vascular endothelial growth factor (VEGF) in the peritoneal fluid and plasma (P < .005); and monocyte chemotactic protein 1 (MCP-1) in the peritoneal fluid (P < .05), (3) highly significant suppression of VEGF expression in the endometriotic tissue (P < .0005); and (4) considerable histological changes in the endometriotic foci following resveratrol treatment.. Resveratrol appears to be effective on the development of endometriosis through its antiangiogenic and anti-inflammatory properties. Future studies with different doses of resveratrol might provide more comprehensive results regarding the treatment of endometriosis.

Topics: Animals; Disease Models, Animal; Endometriosis; Endometrium; Female; Random Allocation; Rats; Rats, Sprague-Dawley; Remission Induction; Resveratrol; Stilbenes

Topics: Animals; Capillaries; Endometriosis; Endometrium; Female; Neovascularization, Pathologic; Stilbenes

To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions.. Intravital microscopic, histologic, and immunohistochemical study.. University institute.. BALB/c mice.. Murine endometriotic lesions were induced by syngeneic transplantation of endometrium into dorsal skinfold chambers. After 6 days, the mice received an intraperitoneal injection of 80 mg/kg CA4P or vehicle.. Vascularization of the lesions and the surrounding tissue was analyzed by intravital fluorescence microscopy over 8 days. Lesion morphology, vessel maturation, viability, and proliferation of endometrial glands and stroma were assessed by histology and immunohistochemistry.. All lesions were initially well vascularized, containing immature and mature microvessels. Injection of CA4P induced a selective vessel collapse in the lesions without affecting the surrounding microvasculature. This resulted in a decreased functional capillary density and blood perfusion of CA4P-treated lesions after 2 hours when compared with controls. However, the vascularization of the lesions progressively normalized, and their numbers of proliferating and apoptotic cells did not differ from those of controls.. This study demonstrates a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for endometriosis therapy.

Topics: Animals; Apoptosis; Capillaries; Cell Proliferation; Disease Models, Animal; Endometriosis; Endometrium; Female; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Stilbenes; Time Factors; Tissue Survival

Can resveratrol and epigallocatechin-3-gallate (EGCG) inhibit the growth and survival of endometriotic-like lesions in vivo in a BALB/c model of endometriosis, and in vitro in primary cultures of human endometrial epithelial cells (EECs)?. Resveratrol and EGCG exerted a potent inhibitory effect on the development of endometriosis in a BALB/c murine model and on the survival of EECs.. Endometriosis is a common condition associated with infertility and pelvic pain in women of reproductive age. Resveratrol and EGCG are two polyphenols with anticarcinogenic and antioxidant properties that have been proposed as natural therapies to treat endometriosis.. Fifty-six 2-month-old female BALB/c mice underwent surgical induction of endometriosis. Treatments with resveratrol or EGCG started 15 days post-surgery and continued for 4 weeks. Human biopsies were taken with a metal Novak curette from the posterior uterine wall from 16 patients with untreated endometriosis and 15 controls who underwent diagnostic laparoscopy for infertility.. After the treatments, animals were sacrificed and lesions were counted, measured, excised and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for cell proliferation and vascularization assessment in the lesions. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique was performed for apoptosis evaluation. Peritoneal fluid was collected to analyze vascular endothelial growth factor levels. Human EECs were purified from proliferative-phase endometrial biopsies and cultured. The effect of both polyphenols on cell proliferation was determined by a colorimetric assay using the CellTiter 96®AQueous One Solution Cell Proliferation Assay kit and on apoptosis by the TUNEL technique, using an In Situ Cell Death Detection Kit with Fluorescein.. In the mouse model, both treatments significantly reduced the mean number (P < 0.05 versus control) and the volume of established lesions (P < 0.05 versus control). Treatments consistently statistically significantly diminished cell proliferation (resveratrol P < 0.01 and EGCG P < 0.05, versus control), reduced vascular density (resveratrol P < 0.01 and EGCG P < 0.001, versus control) and increased apoptosis within the lesions (resveratrol P < 0.01 and EGCG P < 0.05, versus control). Both compounds induced reduction in human EEC proliferation (P < 0.05 versus basal) and increased apoptosis (P < 0.05 versus basal) in primary cultures.. In vitro studies were only carried out in epithelial cells from human eutopic endometrium.. The present findings are promising and will assist the development of novel natural treatments for endometriosis.. This study was supported by ANPCYT (PICT 6384 BID 1201 OC-AR) and CONICET (PIP 5471), Argentina. None of the authors has any conflict of interest to declare.

Topics: Angiogenesis Inhibitors; Animals; Antioxidants; Apoptosis; Catechin; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Endometriosis; Endometrium; Female; Humans; Injections, Intraperitoneal; Intestinal Diseases; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Random Allocation; Resveratrol; Stilbenes

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

Topics: Adolescent; Adult; Animals; Endometriosis; Endometrium; Female; Humans; Mice; Mice, Nude; Middle Aged; Resveratrol; Stilbenes; Stromal Cells; Young Adult

Topics: Analgesics; Endometriosis; Female; Glucosides; Humans; Palmitic Acids; Pelvic Pain; Stilbenes

Endometriosis is a chronic oestrogen-dependent gynaecological disorder, the most common symptom of which is pain. Inflammation can be considered one of the major causes of pain in endometriosis. In particular, degranulating mast cells have been found in significantly greater quantities in endometriotic lesions than in unaffected tissues. The increase in activated and degranulating mast cells is closely associated with nerve structures in painful endometriotic lesions. These observations indicate that inflammation due to mast cells may contribute to the development of pain and hyperalgesia in endometriosis. Controlling mast-cell activation may therefore relieve the pain associated with endometriotic lesions.. Four patients presenting an endometriosis-related pain intensity >or=5 (visual analogue scale for pain, or VAS) were enrolled and monitored during 3 months of the following treatment: oral palmitoylethanolamide 400mg and polydatin 40mg, twice daily for 90 days. Deep dyspareunia, dyschezia, dysuria, dysmenorrhoea and analgesic drug use during the 3-month follow-up period were also monitored, with the aim of demonstrating a reliable reduction in chronic pelvic pain.. The preliminary results indicate that all patients enrolled experienced pain relief as early as 1 month after starting treatment. Furthermore, a reduction in the analgesic drugs usually employed for pain control was observed in all subjects treated. Additionally, some improvements in endometriotic lesions seemed to be demonstrated by imaging.. The palmitoylethanolamide-polydatin combination seems to be very useful in controlling chronic pelvic pain associated with endometriosis. As a result of these findings we have initiated a multi-centre pilot study to verify the effectiveness of this treatment in controlling the chronic pelvic pain associated with endometriosis.

Topics: Adult; Amides; Drug Combinations; Dyspareunia; Endocannabinoids; Endometriosis; Ethanolamines; Female; Glucosides; Humans; Mast Cells; Middle Aged; Palmitic Acids; Pelvic Pain; Stilbenes

Topics: 17-Ketosteroids; Adenocarcinoma; Atrophy; Chorionic Gonadotropin; Clomiphene; Diagnosis; Drug Therapy; Endometriosis; Endometrium; Female; Follicle Stimulating Hormone; Genital Diseases, Female; Gonadotropins; Humans; Hyperplasia; Infertility; Infertility, Female; Ovulation; Pathology; Polycystic Ovary Syndrome; Stilbenes; Toxicology; Urine; Uterine Neoplasms

Topics: Congenital Abnormalities; Endometriosis; Female; Fetal Diseases; Gynecology; Humans; Maternal-Fetal Exchange; Metronidazole; Neoplasms; Obstetrics; Ovarian Neoplasms; Pregnancy; Stilbenes; Trichomonas Vaginitis; Uterine Cervical Neoplasms

Topics: Adenocarcinoma; Amenorrhea; Clomiphene; Endometrial Hyperplasia; Endometriosis; Female; Humans; Menopause; Pathology; Stilbenes