Abstract
In clinical pathology, stent interposition is used to treat vascular disease but can lead to restenosis. Drug-eluting stents (DES) are most commonly used to suppress restenosis but can also have side effects. Therefore, we investigated the anti-proliferative effect and its possible target in vitro and in vivo. We found that Alpinia officinarum Hance (AO) extract efficiently inhibited VSMC proliferation by arresting the transition from the G0/G1 to the S phase via the up-regulation of p27KIP1 expression. Galangin (GA) was determined to be a significant component of this extract, with the same anti-proliferative activity as the raw extract. Immunoblotting and immunofluorescence staining showed that both the AO extract and GA targeted the up-regulation of p27KIP1 expression. Therefore, we next examined the effect of these compounds in a cuff-injured neointimal hyperplasia model in vivo. In this animal model, both the AO extract and GA completely suppressed the neointima formation, and this inhibitory effect was also demonstrated to target the up-regulation of p27KIP1, including the suppression of proliferating cell nuclear antigen expression. Our findings indicate that AO extract and GA have a potent anti-proliferative activity, targeting the up-regulation of p27 expression. Thus, GA may represent an alternative medicine for use in DES.
Highlights
Vascular disease is caused by a number of factors, such as the inflammatory response to vascular injury, neointima hyperplasia by vascular smooth muscle cell (VSMC) proliferation[1]
To determine whether the anti-proliferative activity of Alpinia officinarum Hance (AO) extract was due to cytotoxicity, we examined the cytotoxicity at following treatment with 10, 30, and 50 μg/mL extract for various times using Annexin V-FITC/propidium iodide (PI) staining and a colorimetric WST-1 assay
From the G0/G1 to the S phase of the cell cycle (Fig. 2B). These results indicate that the anti-proliferative effect of the AO extract is correlated with the expression of proteins that cause VSMC proliferation via transitions in the cell cycle, such as cyclin, cyclin-dependent kinases (CDKs), retinoblastoma (Rb) protein, proliferation cell nuclear antigen (PCNA), and CDK inhibitors (CKIs)
Summary
Vascular disease is caused by a number of factors, such as the inflammatory response to vascular injury, neointima hyperplasia by vascular smooth muscle cell (VSMC) proliferation[1]. Vascular balloon dilatation involving stent interposition has been used to treat vascular disease in clinical pathology This stenting can itself lead to restenosis accompanying neointima hyperplasia through the abnormal proliferation of VSMCs2. In this study, we compared the function of AO extract and GA with that of paclitaxel and rapamycin (sirolimus), which is used to treat vascular disease in clinical pathology, on VSMC proliferation, and investigated their targets of action. We verified their therapeutic effects in an animal model resulting from restenosis and atherosclerosis. Our findings suggest that GA has potential as an alternative drug to paclitaxel and rapamycin when treating vascular disorders
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