Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China; Department of Geriatrics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China.
Int Immunopharmacol. 2024 Apr 20;131:111897. doi: 10.1016/j.intimp.2024.111897. Epub 2024 Mar 20.
Esculin, a main active ingredient from Cortex fraxini, possesses biological activities such as anti-thrombosis, anti-inflammatory, and anti-oxidation effects. However, the effects of Esculin on septic cardiomyopathy remains unclear. This study aimed to explore the protective properties and mechanisms of Esculin in countering sepsis-induced cardiac trauma and dysfunction.
In lipopolysaccharide (LPS)-induced mice model, Esculin could obviously improve heart injury and function. Esculin treatment also significantly reduced the production of inflammatory and apoptotic cells, the release of inflammatory cytokines, and the expression of oxidative stress-associated and apoptosis-associated markers in hearts compared to LPS injection alone. These results were consistent with those of in vitro experiments based on neonatal rat cardiomyocytes. Database analysis and molecular docking suggested that TLR4 was targeted by Esculin, as shown by stable hydrogen bonds formed between Esculin with VAL-308, ASN-307, CYS-280, CYS-304 and ASP-281 of TLR4. Esculin reversed LPS-induced upregulation of TLR4 and phosphorylation of NF-κB p65 in cardiomyocytes. The plasmid overexpressing TLR4 abolished the protective properties of Esculin in vitro.
We concluded that Esculin could alleviate LPS-induced septic cardiomyopathy via binding to TLR4 to attenuate cardiomyocyte inflammation, oxidative stress and apoptosis.
秦皮乙素是秦皮的主要活性成分，具有抗血栓、抗炎和抗氧化作用。然而，秦皮乙素对脓毒症性心肌病的作用尚不清楚。本研究旨在探讨秦皮乙素在对抗脓毒症引起的心脏损伤和功能障碍方面的保护作用及其机制。
在脂多糖（LPS）诱导的小鼠模型中，秦皮乙素能明显改善心脏损伤和功能。与 LPS 注射组相比，秦皮乙素治疗组心脏中炎症和凋亡细胞的产生、炎症细胞因子的释放以及氧化应激相关和凋亡相关标志物的表达明显减少。这些结果与基于新生大鼠心肌细胞的体外实验结果一致。数据库分析和分子对接表明，秦皮乙素靶向 TLR4，秦皮乙素与 TLR4 的 VAL-308、ASN-307、CYS-280、CYS-304 和 ASP-281 之间形成稳定的氢键。秦皮乙素逆转了 LPS 诱导的心肌细胞 TLR4 上调和 NF-κB p65 磷酸化。过表达 TLR4 的质粒消除了秦皮乙素在体外的保护作用。
我们得出结论，秦皮乙素通过与 TLR4 结合减轻 LPS 诱导的脓毒症性心肌病，从而减轻心肌细胞炎症、氧化应激和凋亡。
