Abstract

BackgroundKiom-18 is a novel composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra. Curcuma longa and Glycyrrhiza glabra, which are traditional medicines in Asia, have been reported to demonstrate preventive effects against atherosclerosis; however, they have not yet been developed into functional atherosclerosis treatments. We therefore studied the anti-atherosclerotic effects and possible molecular mechanisms of Kiom-18 using vascular smooth muscle cells (VSMCs).MethodsTo assess the anti-proliferative effect of Kiom-18 in vitro, we performed thymidine incorporation, cell cycle progression, immunoblotting and immunofluorescence assays in VSMCs stimulated by platelet derived-growth factor (PDGF)-BB. In addition, we used LDLr knockout mice to identify the effects of Kiom-18 as a preliminary result in an atherosclerosis animal model.ResultsKiom-18 inhibited platelet-derived growth factor (PDGF)-BB-stimulated-VSMC proliferation and DNA synthesis. Additionally, Kiom-18 arrested the cell cycle transition of G0/G1 stimulated by PDGF-BB and its cell cycle-related proteins. Correspondingly, the level of p27kip1 expression was upregulated in the presence of the Kiom-18 extract. Moreover, in an atherosclerosis animal model of LDLr knockout mice, Kiom-18 extract showed a preventive effect for the formation of atherosclerotic plaque and suppressed body weight, fat weight, food treatment efficiency, neutrophil count, and triglyceride level.ConclusionsThese results indicate that Kiom-18 exerts anti-atherosclerotic effects by inhibiting VSMC proliferation via G0/G1 arrest, which upregulates p27Kip1 expression.

Highlights

  • Kiom-18 is a novel composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra

  • Kiom-18 extract at a concentration of 30 and 50 μg/ml significantly inhibited vascular smooth muscle cell (VSMC) proliferation compared with the platelet-derived growth factor (PDGF-BB)-stimulated control (Fig. 1a)

  • To identify the effect of Kiom-18 on VSMC proliferation via early signal transduction pathways, we examined the activation of phospholipase C-γ1 (PLCγ1), phosphatidylinositol 3-kinase-linked protein kinase (Akt), p38, ERK1/2, or c-Jun N-terminal kinase (JNK); no difference was observed in the phosphorylation of early signal pathways in the presence of Kiom-18 (Fig. 1b)

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Summary

Introduction

Kiom-18 is a novel composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra. The topic of this study, Kiom-18, is a novel composition of four herbal components: Chinese cinnamon (Cinnamomum cassia), Japanese red pine (Pinus densiflora), turmeric (Curcuma longa) and licorice (Glycyrrhiza glabra) These four herbal components of Kiom-18 have been previously reported to exhibit beneficial in vitro and in vivo effects as traditional medicines. G. glabra has hepatoprotective effects in combination with glycyrrhizin and silymarin, which are metabolites of G. glabra and milk thistle (Silybum marianum), respectively, and anti-tubercular effects for its extract that includes active compounds [38, 39] Among these individual components of Kiom-18, C. longa and G. glabra have been reported in many studies to prevent atherosclerosis by the suppression of low-density lipoprotein (LDL)

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