Department of Cardiology, 159434Xuzhou Central Hospital, Xuzhou, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211069043. doi: 10.1177/09603271211069043.
Curcumin has been reported to have many benefits, including anti-inflammatory, anti-cancer, and so on. In this research, we aimed to investigate the function of curcumin on lipopolysaccharide (LPS)-injured H9c2 cells.
H9c2 cells stimulated by LPS mimic the in vitro model of myocarditis injury. Comparative Toxicogenomics Database (CTD) was applied to detect the genes associated with curcumin. GEO database was used to analyze Intercellular Adhesion Molecule 1 (ICAM1) and CD40 expression in myocarditis patients. KEGG enrichment analysis was employed to investigate the meaningful pathways related to differentially expressed genes. Cell proliferation, apoptosis, expression of ICAM1/CD40/P65- NF-κB, and level of TNF-α, IL-6, and IL-10 were observed by cell counting kit-8, flow cytometry and western blotting assays, ELISA assay, respectively.
After curcumin treatment, the decreased activity of H9c2 cells evoked by LPS was improved. ICAM1 and CD40, which highly expressed in myocarditis patients, were identified as targets of curcumin and negatively regulated by curcumin. Inhibition of ICAM1 or CD40 strengthened the protective effect of curcumin on LPS-evoked H9c2 cells damage, accompanied by increased cell viability and decreased cell apoptosis and inflammation. Additionally, addition of curcumin or depletion of ICAM1/CD40 suppressed p-P65 NF-κB expression.
Curcumin mitigated LPS-evoked H9c2 cells damage by suppression of ICAM1/CD40/NF-κB, providing a potential molecular mechanism for the clinical application of curcumin.
姜黄素具有许多益处，包括抗炎、抗癌等。在这项研究中，我们旨在研究姜黄素对脂多糖（LPS）损伤的 H9c2 细胞的作用。
用 LPS 刺激的 H9c2 细胞模拟心肌炎损伤的体外模型。比较毒理学基因组数据库（CTD）用于检测与姜黄素相关的基因。GEO 数据库用于分析心肌炎患者中细胞间黏附分子 1（ICAM1）和 CD40 的表达。KEGG 富集分析用于研究与差异表达基因相关的有意义途径。通过细胞计数试剂盒-8、流式细胞术和 Western blot 分析分别观察细胞增殖、凋亡、ICAM1/CD40/P65-NF-κB 的表达以及 TNF-α、IL-6 和 IL-10 的水平。
姜黄素处理后，LPS 诱导的 H9c2 细胞活性降低得到改善。在心肌炎患者中高表达的 ICAM1 和 CD40 被鉴定为姜黄素的靶点，并受姜黄素的负调控。抑制 ICAM1 或 CD40 增强了姜黄素对 LPS 诱导的 H9c2 细胞损伤的保护作用，伴随着细胞活力的增加和细胞凋亡和炎症的减少。此外，添加姜黄素或耗尽 ICAM1/CD40 抑制了 p-P65 NF-κB 的表达。
姜黄素通过抑制 ICAM1/CD40/NF-κB 减轻 LPS 诱导的 H9c2 细胞损伤，为姜黄素的临床应用提供了潜在的分子机制。
