The Action and Mechanism of Action of Icariin on Human Hepatic Sinusoidal Endothelial Cell Senescence: A Laboratory Study

Abstract

Objective: Icariin (ICA) may have an antiaging effect. However, whether this applies to its hepatic cell remains unclear. The aim of this study was to explore the effect and mechanism of action of ICA on hepatic cell senescence. Methods: Serum exosomes isolated from patients with hepatitis B virus-induced liver cirrhosis were utilized to induce senescent phenotypes of human hepatic sinusoidal endothelial cells (HHSECs). ICA, microRNA-22-3p (miR-22-3p) inhibitor and mimic, and sirtuin 1 (SIRT1) overexpression were applied, to investigate the effect of ICA. Senescence-associated β-galactosidase (SA-β-gal) staining, flow cytometry, and quantitative real-time polymerase chain reaction and Western blot were employed to determine cellular senescence, cell cycle progression, and RNA and protein levels, respectively. A dual-luciferase reporter gene assay was performed to validate the binding between miR-22-3p and SIRT1. Results: Serum exosomes significantly promoted the senescent phenotypes of HHSECs, as revealed by the increased SA-β-gal positive cell number and cell cycle arrest at G1 phase. However, ICA significantly reversed these alterations, in a dose-dependent manner. miR-22-3p was shown to target SIRT1. miR-22-3p upregulation significantly promoted cell senescence and significantly downregulated SIRT1 levels, which could be duplicated by overexpressing SIRT1. Furthermore, the suppressive effect of ICA on cellular senescence and its promoting action on upregulating SIRT1 were significantly reversed by overexpressing miR-22-3p. Conclusions: ICA has an anti-aging effect on human hepatic sinusoidal endothelial cells, which is effected through miR-22-3p and its target SIRT1.