Alshareef Nuha Saad, AlSedairy Sahar Abdulaziz, Al-Harbi Laila Naif, Alshammari Ghedeir M, Yahya Mohammed Abdo
Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia.
Antioxidants (Basel). 2024 Sep 10;13(9):1098. doi: 10.3390/antiox13091098.
This study aimed to examine the hepatic and anti-steatotic protective effects of methanolic extract from (safflower) flowers (SFFE), using a rat model of type 2 diabetes mellitus (T2DM), and to examine the molecular mechanisms underlying these effects. Adult male Wistar rats were used for this study. First, T2DM was induced in some rats by feeding them a high-fat diet (HFD) for 4 weeks, followed by a single dose of streptozotocin (STZ) (35 mg/kg, i.p.). Experimental groups included the following five groups (n = 8 in each): control, control + SFFE, T2DM, T2DM + SFFE, and T2DM + SFFE + brusatol (an Nrf2 inhibitor, 2 mg/kg, i.p.). SFFE was administered at a concentration of 300 mg/kg, and all experiments concluded after 8 weeks. Treatments with SFFE significantly reduced fasting blood glucose levels, free fatty acids (FFAs), cholesterol, triglycerides, and low-density lipoprotein cholesterol in both the control and T2DM rats, but they failed to reduce fasting insulin levels in these groups. SFFE treatments also improved the liver structure and reduced hepatocyte vacuolization and hepatic levels of triglycerides and cholesterol in T2DM rats, in addition to increasing the hepatic mRNA levels of keap1 and the cytoplasmic levels and nuclear activities of Nrf2 in both the control and T2DM rats. SFFE also stimulated the expression levels of PPARα and CPT-1 but reduced the malondialdehyde (MDA), mRNA levels of SREBP1, fatty acid synthase, and acetyl CoA carboxylase in both the control and T2DM rats; meanwhile, it reduced hepatic mRNA and the nuclear activities of NF-κB and increased levels of glutathione, superoxide dismutase, and heme oxygenase-1 in the livers of both groups of treated rats. Furthermore, SFFE suppressed the levels of caspase-3, Bax, tumor necrosis factor-α, and interleukin-6 in the T2DM rats. Treatment with brusatol prevented all of these effects of SFFE. In conclusion, SFFE suppresses liver damage and hepatic steatosis in T2DM through Nrf2-dependent hypoglycemic, antioxidant, anti-inflammatory, and hypolipidemic effects.
本研究旨在利用2型糖尿病（T2DM）大鼠模型，研究红花花甲醇提取物（SFFE）的肝脏保护作用和抗脂肪变性保护作用，并探讨其作用的分子机制。本研究使用成年雄性Wistar大鼠。首先，部分大鼠通过高脂饮食（HFD）喂养4周，随后腹腔注射单剂量链脲佐菌素（STZ）（35mg/kg）诱导T2DM。实验组包括以下五组（每组n = 8）：对照组、对照组+SFFE、T2DM组、T2DM+SFFE组和T2DM+SFFE+布沙托（一种Nrf2抑制剂，2mg/kg，腹腔注射）组。SFFE以300mg/kg的浓度给药，所有实验在8周后结束。SFFE处理显著降低了对照组和T2DM大鼠的空腹血糖水平、游离脂肪酸（FFA）、胆固醇、甘油三酯和低密度脂蛋白胆固醇，但未能降低这些组的空腹胰岛素水平。SFFE处理还改善了T2DM大鼠的肝脏结构，减少了肝细胞空泡化以及肝脏甘油三酯和胆固醇水平，此外还增加了对照组和T2DM大鼠肝脏中keap1的mRNA水平以及Nrf2的细胞质水平和核活性。SFFE还刺激了PPARα和CPT-1的表达水平，但降低了对照组和T2DM大鼠的丙二醛（MDA）、SREBP1、脂肪酸合酶和乙酰辅酶A羧化酶的mRNA水平；同时，它降低了肝脏中NF-κB的mRNA和核活性，并增加了两组处理大鼠肝脏中谷胱甘肽、超氧化物歧化酶和血红素加氧酶-1的水平。此外，SFFE抑制了T2DM大鼠中caspase-3、Bax、肿瘤坏死因子-α和白细胞介素-6的水平。布沙托处理可阻止SFFE的所有这些作用。总之，SFFE通过Nrf2依赖性的降糖、抗氧化、抗炎和降血脂作用抑制T2DM中的肝脏损伤和肝脂肪变性。
