Zhao Lisha, Liu Ruifeng, Kang Yutong, Chen Yanying, Xiao Yuchan, Cheng Xiaorong, Zhang Lanlan
Department of Pharmacy, Zhongshan City People's Hospital, No. 2, Sunwendong Road, Zhongshan, 528403, Guangdong Province, People's Republic of China.
Preparation Room, Department of Pharmacy, Hospital of Xinjiang Traditional Uyghur Medicine, Urumqi, 830049, Xinjiang Uygur Autonomous Region, People's Republic of China.
Sci Rep. 2025 May 28;15(1):18761. doi: 10.1038/s41598-025-97964-7.
Hyperlipidemia, characterized by dysregulated lipid metabolism, is a major risk factor for cardiovascular diseases and is often accompanied by oxidative stress. This study aimed to investigated the protective effects and underlying mechanisms of Marein, a primary active flavonoid from Coreopsis tinctoria, in an HO-induced oxidative stress model using HepG2 cells. HepG2 cells was exposed to HO to induce oxidative stress and lipid accumulation, followed by Marein intervention. Cell viability, reactive oxygen species (ROS) levels, and lactate dehydrogenase (LDH) release was assessed using CCK-8, fluorescence microscopy, and ELISA, respectively. Oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), as well as lipid profiles (TC, TG, LDL-C, and HDL-C), were measured. The expression levels of SIRT1, Nrf2, and lipid metabolism-related genes (HMGCR, LDLR) were determined via RT-qPCR and Western blot analysis. The results revealed that Marein treatment significantly restored cell viability, reduced LDH release, and improved antioxidant capacity by lowering ROS and MDA levels while enhancing SOD and GSH-Px activities. Additionally, Marein intervention significantly mitigated lipid accumulation, evidenced by reduced by TC, TG, and LDL-C levels and increased HDL-C levels. Mechanistically, Marein activated the Sirtuin-1 (SIRT1)/Nuclear factor-erythroid-2-related factor 2 (Nrf2) signaling, which was confirmed by the reversal of its protective effects upon treatment with EX-527 (a specific SIRT1 inhibitor). These findings suggested that Marein exerted its antioxidative and lipid-lowering effects via the SIRT1/Nrf2 signaling, highlighting its potential as a therapeutic candidate for hyperlipidemia and related metabolic disorders.
高脂血症以脂质代谢失调为特征，是心血管疾病的主要危险因素，常伴有氧化应激。本研究旨在探讨来自金鸡菊的主要活性黄酮类化合物马蔺子素在HO诱导的HepG2细胞氧化应激模型中的保护作用及潜在机制。将HepG2细胞暴露于HO以诱导氧化应激和脂质积累，随后进行马蔺子素干预。分别使用CCK-8、荧光显微镜和ELISA评估细胞活力、活性氧（ROS）水平和乳酸脱氢酶（LDH）释放。检测氧化应激标志物，包括丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px），以及血脂谱（总胆固醇、甘油三酯、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇）。通过RT-qPCR和蛋白质免疫印迹分析确定沉默信息调节因子1（SIRT1）、核因子E2相关因子2（Nrf2）和脂质代谢相关基因（3-羟基-3-甲基戊二酰辅酶A还原酶、低密度脂蛋白受体）的表达水平。结果显示，马蔺子素处理可显著恢复细胞活力，降低LDH释放，并通过降低ROS和MDA水平，同时增强SOD和GSH-Px活性来提高抗氧化能力。此外，马蔺子素干预显著减轻了脂质积累，表现为总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平降低，高密度脂蛋白胆固醇水平升高。机制上，马蔺子素激活了Sirtuin-1（SIRT1）/核因子E2相关因子2（Nrf2）信号通路，用EX-527（一种特异性SIRT1抑制剂）处理后其保护作用的逆转证实了这一点。这些发现表明，马蔺子素通过SIRT1/Nrf2信号通路发挥其抗氧化和降脂作用，突出了其作为高脂血症及相关代谢紊乱治疗候选药物的潜力。
