Biochemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt.
Pathology Department, Medical Division, National Research Centre, Cairo, Egypt.
Life Sci. 2020 Sep 1;256:118003. doi: 10.1016/j.lfs.2020.118003. Epub 2020 Jun 23.
Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting females. Mechanisms underlying PCOS complicated pathology remain largely unknown, making current treatment only symptomatic. Increasing reports suggest impaired PI3K/AKT/mTOR pathway and tumor necrosis factor-α (TNF-α) levels are involved in cellular proliferation and metabolism-related disorders. However, rare data explored their role in PCOS. Hence, this study investigated TNF-α and pancreatic PI3K/AKT/mTOR levels in PCOS animal model and evaluated their effects on developed pancreatic deficits. Secondly; we explored the impact of nanocurcumin as powerful anti-inflammatory supplement against these developed pancreatic pathologies.
PCOS was induced in rats using letrozole. Nanocurcumin was formulated to increase solubility and bioavailability of curcumin. Transmission electron microscopy (TEM), zeta potential and Infra-red spectroscopy (FT-IR) were used for characterization. Nanocurcumin was orally ingested for 15 days.
PCOS group exhibited significant disturbance in sex hormones, oxidative stress markers, and TNF-α levels as determined by immunoassay. Western blotting revealed significant reduction of PI3K/AKT/mTOR levels leading to impaired insulin sensitivity, decreased β cells function and mass as confirmed by HOMA assessments and immunohistochemistry. Nanocurcumin significantly improved oxidative markers, glucose indices and TNF-α levels. It reinstated PI3K/AKT/mTOR levels, alleviated insulin resistance, and retained islets integrity consequently restoring normal sex hormonal levels.
To the best of our knowledge, the study is the first to report pancreatic role of PI3K/AKT/mTOR and TNF-α in PCOS and the first to demonstrate nanocurcumin promising potential against PCOS-related pancreatic molecular and histological pathologies that can indeed offer better control of the disease.
多囊卵巢综合征（PCOS）是一种广泛存在的影响女性的内分泌疾病。其复杂病理的潜在机制在很大程度上尚不清楚，这使得当前的治疗方法只能治标不治本。越来越多的报告表明，PI3K/AKT/mTOR 通路和肿瘤坏死因子-α（TNF-α）水平的受损与细胞增殖和代谢相关紊乱有关。然而，很少有数据研究它们在 PCOS 中的作用。因此，本研究在 PCOS 动物模型中检测了 TNF-α 和胰腺 PI3K/AKT/mTOR 水平，并评估了它们对胰腺功能障碍的影响。其次；我们探讨了纳米姜黄素作为一种强大的抗炎补充剂对这些已发展的胰腺病理的影响。
使用来曲唑诱导大鼠 PCOS。纳米姜黄素的配方旨在提高姜黄素的溶解度和生物利用度。使用透射电子显微镜（TEM）、zeta 电位和红外光谱（FT-IR）进行表征。大鼠口服纳米姜黄素 15 天。
免疫测定显示，PCOS 组的性激素、氧化应激标志物和 TNF-α 水平显著紊乱。Western blot 显示，PI3K/AKT/mTOR 水平显著降低，导致胰岛素敏感性降低，β细胞功能和质量下降，这一点通过 HOMA 评估和免疫组织化学得到证实。纳米姜黄素显著改善了氧化标志物、葡萄糖指数和 TNF-α 水平。它恢复了 PI3K/AKT/mTOR 水平，缓解了胰岛素抵抗，并保留了胰岛的完整性，从而恢复了正常的性激素水平。
据我们所知，这项研究首次报道了 PCOS 中胰腺 PI3K/AKT/mTOR 和 TNF-α 的作用，也是首次证明纳米姜黄素对 PCOS 相关胰腺分子和组织病理学具有有前途的潜力，这确实可以更好地控制这种疾病。
