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      • KCI등재

        Plantamajoside Attenuates Neointima Formation via Upregulation of Tissue Inhibitor of Metalloproteinases in Balloon-Injured Rats

        임리진,기영재,김현화,추병삼,최인영,최동현,송희상 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.5

        The abnormal change of vascular smooth muscle cell (VSMC) behavior is an important cellular event leading to neointimal hyperplasia in atherosclerosis and restenosis. Plantamajoside (PMS), a phenylethanoid glycoside compound of the Plantago asiatica, has been reported to have anti-inflammatory, antioxidative, and anticancer activities. In this study, the protective effects of PMS against intimal hyperplasia and the mechanisms underlying the regulation of VSMC behavior were investigated. MTT and BrdU assays were performed to evaluate the cytotoxicity and cell proliferative activity of PMS, respectively. Rat aortic VSMC migrations after treatment with the determined concentration of PMS (50 and 150 μM) were evaluated using wound healing and Boyden chamber assays. The inhibitory effects of PMS on intimal hyperplasia were evaluated in balloon-injured (BI) rat carotid artery. PMS suppressed the proliferation in platelet-derived growth factor-BB-induced VSMC, as confirmed from the decrease in cyclin-dependent kinase (CDK)-2, CDK-4, cyclin D1, and proliferating cell nuclear antigen levels. PMS also inhibited VSMC migration, consistent with the downregulated expression and zymolytic activities of matrix metalloproteinase (MMP)2, MMP9, and MMP13. PMS specifically regulated MMP expression through p38 mitogen-activated protein kinase and focal adhesion kinase pathways. Tissue inhibitor of metalloproteinase (TIMP)1 and TIMP2 levels were upregulated via Smad1. TIMPs inhibited the conversion of pro-MMPs to active MMPs. PMS significantly inhibited neointimal formation in BI rat carotid arteries. In conclusion, PMS inhibits VSMC proliferation and migration by upregulating TIMP1 and TIMP2 expression. Therefore, PMS could be a potential therapeutic agent for vascular atherosclerosis and restenosis treatment.

      • KCI등재

        Decaschistia intermedia Craib 추출물의 멜라닌 합성 억제 효능

        임리진,추병삼,이상우,Bounleuane Douangdeuane,송희상 한국생약학회 2020 생약학회지 Vol.51 No.3

        The purpose of this study was to investigate the anti-melanogenic effects of the extracts from Decaschistia intermedia craib (EDI). In this study, we examined the effects of EDI on mushroom tyrosinase activity in in vitro, melanin contents, and expression levels of mRNA and proteins of melanogenesis-related genes in B16F10 melanoma cells. The treatment of EDI significantly decreased both tyrosinase activity and melanin contents in B16F10 cells with dose-dependent manner. In addition, we found that the expression of mRNA or proteins of melanogenic proteins, such as, a-melanocyte-stimulating hormone (a-MSH)-induced microphthalmia associated transcription factor (MITF), tyrosinase, tyrosinase related protein-1 (TRP-1), and TRP-2 was significantly downregulated with dose-dependent manner in the EDI-treated B16F10 cells compared to controls. Our results suggest that the EDI inhibits cellular melanogenesis through downregulation of a-MSH-stimulated melanin synthesis. Thus EDI may potentially be an effective whitening agent.

      • KCI등재

        Dendropanax morbifera Extract Inhibits Intimal Hyperplasia in Balloon-Injured Rat Carotid Arteries by Modulating Phenotypic Changes in Vascular Smooth Muscle Cells

        임리진,조주영,윤상필,장인엽,기영재,최동현,송희상 한국생약학회 2020 Natural Product Sciences Vol.26 No.1

        The plant Dendropanax morbifera Léveille is effective folk medicines for the treatment of several conditions, such as infectious diseases, skin diseases, and other illnesses. Although the inhibitory effects of D. morbifera on the proliferation and migration of vascular smooth muscle cells (VSMCs) have been shown in our previous study, its effects in vivo remain to be elucidated. In this study, we aimed to investigate the protective effects of the extracts from D. morbifera (EDM) on neointimal hyperplasia of rat carotid artery and explore the underlying mechanisms. We observed that the ratio of intima to media thickness (I/M) was significantly decreased in the EDM-treated groups by ~80% compared to that of the control. The expression of Ki-67 and proliferating cell nuclear antigen was decreased by ~70% in the EDM-treated groups compared to that of the control. In addition, matrix metalloproteinase (MMP)2 and MMP9 significantly reduced in the neointimal layer of the EDM-treated groups. Moreover, the decreased levels of contractile phenotypic markers of VSMCs, such as a-smooth muscle actin, myocardin, and smooth muscle-myosin heavy chain, were successfully restored by EDM treatment. Furthermore, the levels of synthetic phenotypic markers, cellular retinal binding protein 1 and connexin 43 were also restored to normal levels. These results suggest that EDM inhibits vascular neointimal hyperplasia induced by balloon injury in rats via phenotypic modulation of VSMCs. Therefore, EDM may be a potential drug candidate for the prevention of restenosis.

      • KCI등재

        천연물의 심혈관질환에 대한 약리적 효과

        임리진(Leejin Lim),박평심(Pyoung Sim Park),송희상(Heesang Song) 대한약학회 2015 약학회지 Vol.59 No.4

        Cardiovascular disease is one of the leading cause of death in many developed countries as well as developing countries. Many evidences indicate that natural products have profound beneficial effects for cardioprotection. In addition to the crude extracts, an identified single compound may be used as a lead molecule for the therapeutic interests. In this review, we discuss promising natural products for cardiovascular diseases, their molecular targets, and their mechanisms, which may help the further direction of studies and applications of natural products for cardiovascular diseases.

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