Galangin reduces vascular endothelial cell dysfunction via Heme oxygenase-1 signaling.

OBJECTIVE: As one of the independent risk factors for atherosclerosis (AS), oxidized low-density lipoprotein (ox-LDL) can trigger damage to the vascular intima and induce the expression of various adhesion molecules. This study aimed to explore the effects of galangin, an extract of galangal, on ox-LDL-induced vascular endothelial cells. METHODS: The effects of different concentrations of galangin or ox-LDL on the metabolic activity of vascular endothelial cells were determined using the CCK8 assay. Afterward, the role of galangin in the expression levels of inflammatory factors was assessed using RT-qPCR and Western blotting. In addition, the influences of galangin on apoptosis and endothelial-mesenchymal transition (EndMT) were also evaluated. Through molecular docking, the Heme oxygenase-1 (HO-1) signaling pathway was proposed, and then the effects of the HO-1 signaling pathway on the regulatory roles of galangin were evaluated. RESULTS: In this study, galangin was found to effectively increase the metabolic activity of ox-LDL-induced cells in a concentration-dependent manner. In addition, galangin was found to reduce ox-LDL-induced cell inflammation, apoptosis, and EndMT. Moreover, galangin could combine with HO-1 and regulate the HO-1 signaling pathway. The effects of galangin on cells were shown to be through the HO-1 signaling pathway. CONCLUSION: To sum up, galangin reduced ox-LDL-induced inflammation, apoptosis, and EndMT of vascular endothelial cells via regulating the HO-1 signaling pathway.

Silencing YY1 Alleviates Ox-LDL-Induced Inflammation and Lipid Accumulation in Macrophages through Regulation of PCSK9/ LDLR Signaling.

The formation of macrophage foam cells stimulated by oxidized low-density lipoprotein (ox-LDL) is deemed an important cause of atherosclerosis. Transcription factor Yin Yang 1 (YY1), which is a universally expressed multifunctional protein, is closely related to cell metabolism disorders such as lipid metabolism, sugar metabolism, and bile acid metabolism. However, whether YY1 is involved in macrophage inflammation and lipid accumulation still remains unknown. After mouse macrophage cell line RAW264.7 cells were induced by ox-LDL, YY1 and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions were found to be increased while low-density lipoprotein receptor (LDLR) expression was lowly expressed. Subsequently, through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, Oil Red O staining and cholesterol quantification, it turned out that silencing of YY1 attenuated the inflammatory response and lipid accumulation in RAW264.7 cells caused by ox-LDL. Moreover, results from the JASPAR database, chromatin immunoprecipitation (ChIP) assay, luciferase reporter assay and Western blot analysis suggested that YY1 activated PCSK9 by binding to PCSK9 promoter and modulated the expression of LDLR in the downstream of PCSK9. In addition, the results of functional experiments demonstrated that the inhibitory effects of YY1 interference on ox-LDL-mediated macrophage inflammation and lipid accumulation were reversed by PCSK9 overexpression. To sum up, YY1 depletion inhibited its activation of PCSK9, thereby reducing cellular inflammatory response, cholesterol homeostasis imbalance, and lipid accumulation caused by ox-LDL.

CSN5 silencing reverses sorafenib resistance of human hepatocellular carcinoma HepG2 cells.

Hepatocellular carcinoma (HCC) is one of the most common tumor types, and is the third leading cause of cancer mortalities worldwide. A large number of patients with HCC are diagnosed at a late stage when the curative treatment of surgical resection and liver transplantation are no longer applicable. Sorafenib has been proved to improve overall survival in advanced HCC; however, drug resistance is common. The present study reported that the CSN5 is correlated with sorafenib resistance of the HCC cell line HepG2/S. Following silencing of CSN5, resistance to sorafenib was reversed, and multi-drug­resistance proteins, including as adenosine triphosphate binding cassette (ABC)B1, ABCC2 and ABCG2 as well as CDK6, cyclin D1 and B­cell lymphoma 2 were downregulated. In addition, it was demonstrated that the integrin beta-1, transforming growth factor­ß1 and nuclear factor­κB pathways were modified by CSN5.