Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Anatomical Histopathology, East Jeddah General Hospital, Jeddah 22253, Saudi Arabia.
Nutrients. 2022 Apr 30;14(9):1891. doi: 10.3390/nu14091891.
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.
子宫内膜增生症（EH）是女性子宫内膜恶性肿瘤的最常见危险因素。EH 的发病机制与子宫炎症直接相关，炎症可导致异常细胞分裂和细胞凋亡减少。白皮杉醇（PIC）是一种天然多酚二苯乙烯，具有抗炎、抗氧化和抗增殖作用。本研究旨在探讨 PIC 对苯甲酸雌二醇（EB）诱导的大鼠 EH 的潜在预防作用。制备了自微乳药物传递系统（SNEDDS）以提高 PIC 的溶解度。因此，将 30 只雌性 Wistar 大鼠分为五组：（1）对照组，（2）PIC SNEDDS（10mg/kg），（3）EB（0.6mg/kg），（4）EB+PIC SNEDDS（5mg/kg）和（5）EB+PIC SNEDDS（10mg/kg）。PIC SNEDDS 的给药可预防 EB 诱导的子宫重量增加和组织病理学变化。此外，它在子宫内膜中表现出促凋亡和抗氧化活性。与 PIC SNEDDS 共同处理的子宫切片的免疫组织化学染色显示肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和核转录因子-κB（NF-κB）的表达明显降低。Nrf2 和血红素加氧酶-1（HO-1）表达的显著增加进一步证实了这种抗炎作用。这些结果表明，PIC 的 SNEDDS 纳米制剂对实验诱导的 EH 具有保护作用。
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