College of Basic Medical Science, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, China.
Toxicol Appl Pharmacol. 2024 Nov;492:117109. doi: 10.1016/j.taap.2024.117109. Epub 2024 Sep 19.
Hydroxysafflor yellow A (HSYA) is the main water-soluble compound of safflower. It is commonly used in liver disease treatment and has anti-osteoporotic activity. However, the specific mechanism of HSYA is not yet fully understood. Thioacetamide (TAA) has toxic effects on the liver and is widely used in establishing animal models of cirrhosis and liver fibrosis. In research of liver-related diseases and bone deformation in vivo, the zebrafish has become a frequently utilized animal model. In establishing a TAA-induced zebrafish liver injury model, we found that TAA-induced zebrafish also developed osteopenia. The aim of our study is to investigate the protective effect of HSYA on TAA-induced liver injury and osteopenia in zebrafish. The findings demonstrated that HSYA alleviated hepatic oxidative stress, inhibited the release of inflammatory factors, and promoted in vivo skeletal mineralization in zebrafish larvae. Further Real-time Polymerase Chain Reaction and Western blotting analyses showed that HSYA altered the expression levels of SIRT1, HMGB1, TLR4, MYD88 and NF-ΚB, ameliorated TAA-induced liver injury, reduced the release of inflammation-related factors IL-6, IL-1β, TNF-α, regulated the ratio of RANKL/OPG, ameliorated TAA-induced osteopenia. In conclusion, our study demonstrated that HSYA exhibited a noteworthy beneficial influence on TAA-induced liver injury and osteopenia in zebrafish, this finding provide a foundation for the application of HSYA in clinical research.
羟基红花黄色素 A（HSYA）是红花的主要水溶性化合物。它常用于治疗肝脏疾病，具有抗骨质疏松活性。然而，HSYA 的具体机制尚未完全了解。硫代乙酰胺（TAA）对肝脏有毒性作用，广泛用于建立肝硬化和肝纤维化的动物模型。在肝脏相关疾病和骨骼变形的体内研究中，斑马鱼已成为常用的动物模型。在建立 TAA 诱导的斑马鱼肝损伤模型时，我们发现 TAA 诱导的斑马鱼也出现了骨质疏松症。本研究旨在探讨 HSYA 对 TAA 诱导的斑马鱼肝损伤和骨质疏松症的保护作用。研究结果表明，HSYA 减轻了肝氧化应激，抑制了炎症因子的释放，并促进了斑马鱼幼虫体内骨骼矿化。进一步的实时聚合酶链反应和 Western blot 分析表明，HSYA 改变了 SIRT1、HMGB1、TLR4、MYD88 和 NF-ΚB 的表达水平，改善了 TAA 诱导的肝损伤，减少了与炎症相关的因子 IL-6、IL-1β、TNF-α 的释放，调节了 RANKL/OPG 的比值，改善了 TAA 诱导的骨质疏松症。总之，本研究表明 HSYA 对 TAA 诱导的斑马鱼肝损伤和骨质疏松症具有显著的有益影响，这一发现为 HSYA 在临床研究中的应用提供了基础。
