Xanthohumol Blocks Proliferation and Migration of Vascular Smooth Muscle Cells in Vitro and Reduces Neointima Formation in Vivo

• Published in: Journal of natural products (Washington, D.C.) Vol. 80; no. 7; pp. 2146 - 2150
• Main Authors: Liu, Rongxia, Heiss, Elke H, Schachner, Daniel, Jiang, Baohong, Liu, Wanhui, Breuss, Johannes M, Dirsch, Verena M, Atanasov, Atanas G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 28.07.2017
• Subjects: Animals; Becaplermin; Cell Movement; Cell Proliferation; chalcone; Disease Models, Animal; Dose-Response Relationship, Drug; Flavonoids - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; hops; Humulus - chemistry; inhibitory concentration 50; MAP Kinase Signaling System; Mice; Molecular Structure; Muscle, Smooth, Vascular - metabolism; myocytes; Myocytes, Smooth Muscle - metabolism; Neointima - chemically induced; Neointima - metabolism; Oxazines - metabolism; Phosphorylation; platelet-derived growth factor; Platelet-Derived Growth Factor - drug effects; Propiophenones - chemistry; Propiophenones - isolation & purification; Propiophenones - pharmacology; Proto-Oncogene Proteins c-sis; Rats; Rats, Sprague-Dawley; Signal Transduction; smooth muscle; Wound Healing - drug effects; Xanthenes - metabolism
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.7b00268

Xanthohumol (1) is a principal prenylated chalcone found in hops. The aim of this study was to examine its influence on platelet-derived growth factor (PDGF)-BB-triggered vascular smooth muscle cell (VSMC) proliferation and migration in vitro and on experimentally induced neointima formation in vivo. Quantification of resazurin conversion indicated that 1 can inhibit PDGF-BB-induced VSMC proliferation concentration-dependently (IC50 = 3.49 μM). Furthermore, in a wound-healing assay 1 potently suppresses PDGF-BB-induced VSMC migration at 15 μM. Tested in a mouse femoral artery cuff model, 1 significantly reduces neointima formation. Taken together, we show that 1 represses PDGF-BB-induced VSMC proliferation and migration in vitro as well as neointima formation in vivo. This novel activity suggests 1 as an interesting candidate for further studies addressing a possible therapeutic application to counteract vascular proliferative disease.