Introduction and aims

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.

Methods

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.

Findings

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.

Significance

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.

中文翻译：

---

纳米姜黄素减轻多囊卵巢综合征大鼠的胰岛素抵抗和胰腺功能衰竭：对PI3K / AkT / mTOR和TNF-α调节的见解。

介绍和目的

多囊卵巢综合征（PCOS）是一种广泛影响女性的内分泌疾病。导致PCOS复杂病理的潜在机制在很大程度上仍然未知，使得目前的治疗仅是对症治疗。越来越多的报道表明，PI3K / AKT / mTOR通路受损，肿瘤坏死因子-α（TNF-α）水平与细胞增殖和代谢相关疾病有关。但是，很少有数据探讨了它们在PCOS中的作用。因此，本研究调查了PCOS动物模型中的TNF-α和胰腺PI3K / AKT / mTOR水平，并评估了它们对发展的胰腺缺陷的影响。其次; 我们探索了纳米姜黄素作为强大的消炎补充剂对这些发达的胰腺病理的影响。

方法

使用来曲唑在大鼠中诱导PCOS。配制纳米姜黄素以增加姜黄素的溶解度和生物利用度。透射电子显微镜（TEM），ζ电位和红外光谱（FT-IR）用于表征。纳米姜黄素经口摄入15天。

发现

通过免疫测定，PCOS组在性激素，氧化应激标记物和TNF-α水平方面表现出明显的紊乱。Western印迹显示HOMA评估和免疫组织化学证实PI3K / AKT / mTOR水平显着降低，导致胰岛素敏感性受损，β细胞功能和质量降低。纳米姜黄素可显着改善氧化标记，葡萄糖指数和TNF-α水平。它恢复了PI3K / AKT / mTOR水平，减轻了胰岛素抵抗，并保留了胰岛的完整性，从而恢复了正常的性激素水平。

意义

据我们所知，该研究是第一个报告PI3K / AKT / mTOR和TNF-α在PCOS中的胰腺作用，并且是第一个证明纳米姜黄素有潜力对抗PCOS相关的胰腺分子和组织病理学，确实可以提供更好的胰腺癌作用控制疾病。