Alsaedi Abdullah Q, Nader Manar A, El-Kashef Dalia H, Abdelmageed Marwa E
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Quality and Output Control, Branch of Ministry of Health, Madinah, Saudi Arabia.
Front Pharmacol. 2025 May 8;16:1572758. doi: 10.3389/fphar.2025.1572758. eCollection 2025.
Insulin resistance (IR) is a hazard to human health in which peripheral insulin-target organs, like the liver, become less sensitive to normal levels of insulin. Dexamethasone (DEX)-induced IR is a distinct model of IR. Hence, the present study investigates the efficacy of mangiferin (Mang) in the reversal of DEX-induced IR in the livers and aortas of rats.
Rats were randomly assigned into six groups: control (CTRL), Mang, DEX, and three pretreated groups (received Mang 25 mg/kg, 50 mg/kg, or 100 mg/kg, orally for 14 days, with DEX (1 mg/kg) injected from day 8 to day 14). On day 15, serum, liver, and aorta tissues were obtained and examined using biochemical, histological, and immunohistochemical assessments.
Mang administration attenuated DEX-induced IR, evidenced by decreased oral glucose tolerance test (OGTT) and fasting serum insulin levels, in addition to improving the DEX-induced hepatic and aortic histopathological alterations. Additionally, Mang attenuated DEX-induced alterations in liver function parameters and improved serum lipid profiles, oxidative stress, and antioxidant biomarkers. Mang also markedly increased hepatic and aortic levels of insulin receptor substrate 1 (IRS1), protein kinase B (AKT), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor-gamma (PPAR-γ) levels. Mang reduced hepatic and aortic tumor necrosis factor-alpha (TNF-α), forkhead box protein O1 (FOXO-1), hepatic NOD-like receptor family pyrin domain-containing 3 (NLRP3), phosphoenol pyruvate carboxy kinase (PEPCK), and glucose 6-phosphatase (G6Pase). Mang elevated hepatic glycogen synthase kinase3 (GSK3α) and glycogen synthase (GS2) levels. Furthermore, Mang ameliorated aortic expression levels of endothelin-1 (ET-1), vascular cell adhesion molecule-1 (VCAM), c-Jun N-terminal kinase (JNK), nuclear factor kappa B (NF-κB), and vascular endothelial growth factor (VEGF) and increased endothelial nitric oxide synthase (eNOS) and prostacyclin (PGI2) levels.
Mang administration could confer hepato- and vasculo-protective activity via its hypolipidemic, hepatoprotective, anti-inflammatory, and antioxidant efficacy.
胰岛素抵抗（IR）对人类健康构成危害，在此过程中，肝脏等外周胰岛素靶器官对正常水平的胰岛素变得不敏感。地塞米松（DEX）诱导的IR是一种独特的IR模型。因此，本研究探讨了芒果苷（Mang）对逆转大鼠肝脏和主动脉中DEX诱导的IR的疗效。
将大鼠随机分为六组：对照组（CTRL）、芒果苷组、DEX组和三个预处理组（分别口服25mg/kg、50mg/kg或100mg/kg芒果苷，持续14天，从第8天至第14天注射DEX（1mg/kg））。在第15天，获取血清、肝脏和主动脉组织，并通过生化、组织学和免疫组织化学评估进行检测。
给予芒果苷可减轻DEX诱导的IR，口服葡萄糖耐量试验（OGTT）和空腹血清胰岛素水平降低证明了这一点，此外还改善了DEX诱导的肝脏和主动脉组织病理学改变。此外，芒果苷减轻了DEX诱导的肝功能参数改变，改善了血清脂质谱、氧化应激和抗氧化生物标志物。芒果苷还显著提高了肝脏和主动脉中胰岛素受体底物1（IRS1）、蛋白激酶B（AKT）、AMP激活的蛋白激酶（AMPK）和过氧化物酶体增殖物激活受体γ（PPAR-γ）的水平。芒果苷降低了肝脏和主动脉中肿瘤坏死因子-α（TNF-α）、叉头框蛋白O1（FOXO-1）、肝脏含NOD样受体家族吡咯结构域3（NLRP3）、磷酸烯醇式丙酮酸羧激酶（PEPCK）和葡萄糖6磷酸酶（G6Pase）的水平。芒果苷提高了肝脏糖原合酶激酶3（GSK3α）和糖原合酶（GS2）的水平。此外，芒果苷改善了主动脉中内皮素-1（ET-1）、血管细胞黏附分子-1（VCAM）、c-Jun氨基末端激酶（JNK）、核因子κB（NF-κB）和血管内皮生长因子（VEGF）的表达水平，并提高了内皮型一氧化氮合酶（eNOS）和前列环素（PGI2）的水平。
给予芒果苷可通过其降血脂、保肝、抗炎和抗氧化作用赋予肝脏和血管保护活性。
