Cudratricusxanthone A Isolated from the Root Bark of Cudrania tricuspidata Inhibits the Proliferation of Vascular Smooth Muscle Cells through the Suppression of PDGF-Receptor Beta Tyrosine Kinase

Abstract

Cudrania tricuspidata (Moraceae) is a deciduous trees widely distributed in Korea, China, and Japan. The cortex and root bark of this species have been used as a traditional medicine for the treatment of neuritis and inflammation. 1) Moreover, the pharmacological study showed that the crude extract from the roots of C. tricuspidata could inhibit the growth of human cancer cell line.2) However, the antiproliferative effect of cudratricusxanthone A isolated from the root bark of C. tricuspidata on vascular smooth muscle cells (VSMCs) is not understood.The abnormal migration and proliferation of VSMCs in arterial walls are important pathogenetic factors of vascular disorders such as atherosclerosis and restenosis after angioplasty.3) Although several growth factors and cytokines are involved in the development of atherosclerotic lesions, one of the principal regulators of mitogenesis in VSMCs is platelet derived growth factor (PDGF)-BB, and that the expression of PDGF-BB is increased in atherosclerotic lesions. In addition, PDGF-BB-induced mitogenesis and proliferation are also known to be prerequisites of intimal thickening, which is invariably observed after angioplasty. 4)The PDGF-BB-induced mitogenesis signaling pathway has already been relatively well characterized. The binding of PDGF-BB to PDGF-receptor (PDGF-R) leads to phosphorylation of PDGF-R beta chain (PDGF-Rb) tyrosine residues. This activated PDGF-Rb is associated with a number of SH2 domain-containing proteins, including the phospholipase C (PLC)g1.5) PDGF-BB activates the extracellular regulated kinases 1 and 2 (ERK1/2) by triggering the activation of RasRaf-MEK, and its activation is known to be associated with the development and progression of proliferative cardiovascular diseases, such as hypertension and atherosclerosis. 6,7) Therefore, an understanding of its inhibition on PDGF-BBstimulated VSMC proliferation is important in terms of developing methods of treating cardiovascular disease.In the present study, we aimed to elucidate the antiproliferative effect and the molecular mechanism of cudratricusxanthone A isolated from the root bark of C. tricuspidata in PDGF-BB-stimulated signaling pathways.

Cudratricusxanthone A from Cudrania tricuspidata suppresses pro-inflammatory mediators through expression of anti-inflammatory heme oxygenase-1 in RAW264.7 macrophages

“…C. tricuspidata and similar species contain biologically active isoprenylated xanthones that are known to have a variety of biological activities, such as anti-tumor-promoting activity, hypertensive effect, anti-viral activity and so on [19,26]. CTXA, an isoprenylated xanthone from C. tricuspidata is known to possess a variety of pharmacological effects [19][20][21][22]. In the present study, we investigated the possible involvement of HO-1 in the anti-inflammatory activities afforded by CTXA, one of the constituents isolated from C. tricuspidata with various biological activities.…”

“…The root bark of this species has been used as a traditional Chinese medicine for the treatment of lumbago, hemoptysis, and contusion [19]. Cudratricusxanthone A (CTXA), isolated from the roots of C. tricuspidata has potent hepatoprotective, anti-proliferative, and mono-amine oxidase inhibitory effects [20][21][22]. CTXA can also scavenge oxygen radicals such as hydroxyl radicals and superoxide [20,23].…”

Anti-Proliferative Effect of an Aqueous Extract ofPrunella vulgarisin Vascular Smooth Muscle Cells

“…The cell migration assay was evaluated by wound healing assay [23]. Briefly, HASMCs on the 12-well culture plates were incubated approximately 80% confluent and then made a scratch with yellow tip.…”

In vitro inhibition of human cytochrome P450 by cudratricusxanthone A

“…Cudratricusxanthone A (CTXA, Fig. 1), isolated from the roots of C. tricuspidata Bureau, has potent antiproliferative, antioxidant, hepatoprotective, and neuroprotective activities (Jeong et al, 2008;Kim et al, 2007;Lee et al, 2006;Tian et al, 2005). Moreover, the antiplatelet, anticoagulant, and profibrinolytic properties of CTXA have been studied in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (Yoo et al, 2013).…”