stilbenes and Endometrial-Hyperplasia

Endometrial hyperplasia (EH) is the most common risk factor for endometrial malignancy in females. The pathogenesis of EH has been directly linked to uterine inflammation, which can result in abnormal cell division and decreased apoptosis. Piceatannol (PIC), a natural polyphenolic stilbene, is known to exert anti-inflammatory, antioxidant and anti-proliferative activities. The aim of the present study was to examine the potential preventive role of PIC in estradiol benzoate (EB)-induced EH in rats. A self-nanoemulsifying drug delivery system (SNEDDS) was prepared to improve the solubility of the PIC. Therefore, thirty female Wistar rats were divided into five groups: (1) control, (2) PIC SNEDDS (10 mg/kg), (3) EB (0.6 mg/kg), (4) EB + PIC SNEDDS (5 mg/kg) and (5) EB + PIC SNEDDS (10 mg/kg). The administration of PIC SNEDDS prevented EB-induced increases in uterine weights and histopathological changes. Additionally, it displayed pro-apoptotic and antioxidant activity in the endometrium. Immunohistochemical staining of uterine sections co-treated with PIC SNEDDS showed significantly decreased expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nuclear transcription factor-kappa B (NF-κB). This anti-inflammatory effect was further confirmed by a significant increase in Nrf2 and heme oxygenase-1 (HO-1) expression. These results indicate that SNEDDS nanoformulation of PIC possesses protective effects against experimentally induced EH.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Endometrial Hyperplasia; Estradiol; Female; Heme Oxygenase-1; Humans; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar; Stilbenes

Resveratrol (Res), a polyphenol that is abundant in many medicinal plants and is a selective oestrogen receptor modulator, exhibits multiple biological activities. In the present study, we determined whether Res prevents oestrogen deficiency-induced osteopenia and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with oestradiol replacement therapy (ERT). A total of sixty 3-4-month-old female Wistar rats were randomly divided into a sham-operated group (Sham) and five ovariectomy (OVX) subgroups, i.e. OVX rats as a control group (OVX); OVX rats receiving oestradiol valerate (ERT, 0·8 mg/kg); and OVX rats receiving Res 20, 40 and 80 mg/kg. Daily oral administration was initiated at week 2 after OVX for 12 weeks. A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture. Only at the highest dose, bone loss was almost equivalent to that observed in the ERT group. The dose-response effects of Res on the biochemical parameters (alkaline phosphatase, IL-6, TNF-α and transforming growth factor-β1 concentrations in the serum as well as urinary Ca and P excretion) and the expressions of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL:osteoprotegerin protein ratio in the femur were also observed. Furthermore, the thickening of the endometrium and the infiltration of lymphocytes were prevented in all the three Res-treated groups compared with the ERT group. In conclusion, Res treatment not only improves BMD and trabecular microarchitecture but also does not affect the uterus and Res might be a potential remedy for the treatment of postmenopausal osteoporosis.

Topics: Animals; Antioxidants; Biomarkers; Bone Density; Bone Density Conservation Agents; Dietary Supplements; Disease Models, Animal; Endometrial Hyperplasia; Endometrium; Estrogen Replacement Therapy; Female; Femur; Humans; Osteoporosis, Postmenopausal; Osteoprotegerin; Phytoestrogens; Random Allocation; RANK Ligand; Rats; Rats, Wistar; Resveratrol; Stilbenes; Time Factors

Topics: Adult; Clomiphene; Cysts; Endometrial Hyperplasia; Female; Humans; Menopause; Middle Aged; Ovary; Ovulation; Stilbenes

Topics: Carcinoma; Endometrial Hyperplasia; Endometrium; Female; Humans; Menopause; Stilbenes; Uterine Neoplasms

Topics: Carcinoma; Carcinoma, Squamous Cell; Clomiphene; Endometrial Hyperplasia; Female; Hemorrhage; Humans; Metrorrhagia; Pathology; Stilbenes; Uterine Neoplasms

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

Topics: Amenorrhea; Clomiphene; Drug Therapy; Endometrial Hyperplasia; Female; Fertilization; Humans; Infertility; Infertility, Female; Menstruation Disturbances; Stilbenes; Toxicology

Topics: Amenorrhea; Disease; Endometrial Hyperplasia; Endometrium; Female; Humans; Stilbenes