Swietenine Alleviates Nonalcoholic Fatty Liver Disease in Diabetic Mice via Lipogenesis Inhibition and Antioxidant Mechanisms.
Swietenine Alleviates Nonalcoholic Fatty Liver Disease in Diabetic Mice via Lipogenesis Inhibition and Antioxidant Mechanisms.
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DOI：
10.3390/antiox12030595
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发表时间：
2023-02-27
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我们以前的研究已经报道了狼毒藤碱(大叶狼毒种子的主要生物活性成分)逆转和增强二甲双胍对糖尿病大鼠高血糖和高脂血症的作用。此外，我们还报道了斯匹林的抗炎作用是通过激活核因子红系相关因子2(NRF2)来实现的。本研究以高脂饮食/链脲佐菌素诱导的糖尿病小鼠为模型，评价了斯匹林对非酒精性脂肪性肝病(NAFLD)的治疗作用及其机制。通过检测血液生化指标(葡萄糖、胆固醇、甘油三酯、丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷胱甘肽(GSH)、总抗氧化能力(TAC)、丙二醛(MDA))和肝脏生化指标(肝指数、胆固醇、甘油三酯)来评价其疗效。脂肪堆积(NAFLD的初始致病因素)用油O红染色确定。采用基因表达(QPCR)和免疫组织化学方法探讨斯匹林治疗NAFLD的作用机制。确定了参与脂肪形成的关键调控因子(ACly、Acc1、Fasn、SREBP1c和ChREBPβ)和氧化应激(NRF2、NQO-1和HO-1)途径。在喂食高脂饮食并注射链脲佐菌素的小鼠中，肝脏胆固醇、甘油三酯和血脂都升高了。每隔一天口服80毫克/千克体重的斯匹列汀，连续8周，逆转了这些增加。基因表达和免疫组织化学研究表明，斯威特宁逆转了脂肪生成关键酶(ACly、Acc1和Fasn)及其主要转录因子(SREBP1c和ChREBPβ)水平的升高。此外，Swetenine激活了Nrf2抗氧化防御机制，Nrf2、NQO-1和HO-1的上调证明了这一点。结论：蛇床子素通过抑制脂肪生成和激活Nrf2途径对糖尿病所致的NAFLD有一定的治疗作用。
Our previous studies have reported the effect of swietenine (a major bioactive component of Swietenia macrophylla seeds) in reversing and potentiating the effect of metformin in hyperglycemia and hyperlipidaemia in diabetic rats. Moreover, we reported that the anti-inflammatory effect of swietenine is mediated via the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This study evaluated the effect of swietenine and its mechanisms in nonalcoholic fatty liver disease (NAFLD) in high-fat diet/streptozotocin-induced diabetic mice. The effect was assessed by determining blood biochemical parameters (glucose, cholesterol, triglycerides, alanine transaminase (ALT), asparate transaminase (AST), alkaline phosphatase (ALP), glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA)) and liver biochemical parameters (liver index, cholesterol, and triglycerides). Hepatic lipid accumulation (initial causative factor in NAFLD) was determined by oil-O-red staining. Gene expression (qPCR) and immunohistochemical studies were performed to elucidate the mechanism of swietenine’s effect in NAFLD. The critical regulators (genes and proteins) involved in lipogenesis (ACLY, ACC1, FASN, SREBP1c, and ChREBPβ) and oxidative stress (Nrf2, NQO-1 and HO-1) pathways were determined. In mice fed with a high-fat diet followed by streptozotocin injection, the liver cholesterol, triglycerides, and lipids were elevated. These increases were reversed by the oral administration of swietenine, 80 mg/kg body weight, on alternate days for eight weeks. Gene expression and immunohistochemical studies showed that swietenine reversed the elevated levels of crucial enzymes of lipogenesis (ACLY, ACC1 and FASN) and their master transcription factors (SREBP1c and ChREBPβ). Furthermore, swietenine activated the Nrf2 antioxidant defense mechanism, as evidenced by the upregulated levels of Nrf2, NQO-1, and HO-1. It is concluded that swietenine shows beneficial effects in diabetes-induced NAFLD via inhibiting lipogenesis and activating the Nrf2 pathway.
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