扁柏黄酮 (HF) 属于黄酮类化合物，是侧柏和卷柏中的主要生物活性化合物。 HF 表现出的活性包括抗 HIV、抗炎、抗病毒、抗氧化和抗肿瘤作用。本研究旨在探讨HF对乙酰氨基酚(APAP)所致急性肝损伤的作用及机制。结果表明，HF 处理减轻了 APAP 对活力的影响，恢复了 HepG2 细胞的 MDA、GSH 和 SOD 水平。 APAP 刺激的 HepG2 细胞中活性氧 (ROS) 线粒体膜电位 (MMP) 的积累也被 HF 阻断。 HF 降低了促凋亡和促焦亡蛋白的水平。流式细胞术分析和荧光染色结果与蛋白质印迹分析一致。在 APAP 诱导的细胞模型中进行 HF 处理后，观察到 Stat3 磷酸化增强和 SIX4 表达增加。然而，不仅通过siRNA沉默了HepG2细胞中的SIX4蛋白，而且添加了Stat3抑制剂（Stattic），显着减弱了HF的抗凋亡和抗焦亡作用。此外，HF 减轻了 C57BL/6 小鼠模型的肝损伤。总体而言，我们的研究表明，在体内和体外，HF 通过 SIX4/Akt/Stat3 通路减轻药物性肝损伤 (DILI) 中 APAP 诱导的细胞凋亡和焦亡。心力衰竭 (HF) 在治疗 DILI 方面可能具有广阔的前景。版权所有 © 2024。由 Elsevier Inc. 出版。

Hinokiflavone (HF), classified as a flavonoid, is a main bioactive compound in Platycladus orientalis and Selaginella. HF exhibits activities including anti-HIV, anti-inflammatory, antiviral, antioxidant and anti-tumor effects. The study aimed to explore the function and the mechanisms of HF on acetaminophen (APAP)-induced acute liver injury. Results indicated that HF treatment mitigated the impact of APAP on viability and restored levels of MDA, GSH and SOD on HepG2 cells. The accumulation of reactive oxygen species (ROS) mitochondrial membrane potential (MMP) in HepG2 cells stimulated by APAP were also blocked by HF. HF reduced the levels of pro-apoptotic and pro-pyroptotic proteins. Flow cytometry analysis and fluorescence staining results were consistent with western blot analysis. Following HF treatment in the APAP-induced cell model, there was observed an augmentation in the phosphorylation of Stat3 and an increase in the expression of SIX4. However, not only silenced the SIX4 protein in HepG2 cells by siRNA, but also adding the Stat3 inhibitor (Stattic), attenuated the anti-apoptotic and anti-pyroptotic effects of HF significantly. Furthermore, HF alleviated liver damage in C57BL/6 mice model. Overall, our study demonstrated that HF mitigates apoptosis and pyroptosis induced by APAP in drug-induced liver injury (DILI) through the SIX4/Akt/Stat3 pathway in vivo and in vitro. HF may have promising potential for for the treatment of DILI.Copyright © 2024. Published by Elsevier Inc.