芒果苷减轻大鼠地塞米松诱导的胰岛素抵抗：对血管功能障碍和肝脂肪变性的深入研究

Mangiferin mitigates dexamethasone-induced insulin resistance in rats: insight into vascular dysfunction and hepatic steatosis.

作者信息

Alsaedi Abdullah Q, Nader Manar A, El-Kashef Dalia H, Abdelmageed Marwa E

机构信息

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.

出版信息

Front Pharmacol. 2025 May 8;16:1572758. doi: 10.3389/fphar.2025.1572758. eCollection 2025.

DOI:10.3389/fphar.2025.1572758

PMID:40406487

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12095298/

Abstract

AIM

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.

MAIN METHODS

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.

KEY FINDINGS

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.

CONCLUSION

Mang administration could confer hepato- and vasculo-protective activity via its hypolipidemic, hepatoprotective, anti-inflammatory, and antioxidant efficacy.

摘要

目的

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。

主要方法

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。

主要发现

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。