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Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression
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논문 기본 정보

Type
Academic journal
Author
Young-Ju Lim (Department of Biotechnology College of Engineering Daegu University Gyeongsan Korea.Research instit) Hyeon Young Min (대구대학교) JangWon-Gu (대구대학교)
Journal
한국지질동맥경화학회(구 한국지질학회) 지질·동맥경화학회지 지질·동맥경화학회지 제10권 제1호 KCI Accredited Journals
Published
2021.1
Pages
62 - 73 (12page)

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Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression
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Abstract· Keywords

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Objective Vascular calcification requires the differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. This phenomenon can be enhanced by inflammation and oxidative stress. Zingerone is one of the active ingredients present in the ginger plant that has anti-inflammatory and antioxidant effects. Other functions include anti-obesity, anti-nausea effects. However, the functions of zingerone on vascular calcification has not yet been elucidated. This study investigated the effect of zingerone on vascular calcification and its molecular mechanism. Methods Reverse transcription-polymerase chain reaction (PCR), real-time PCR and Western blot analysis was used to measure expression levels of osteogenic marker genes and to investigate whether calcification was regulated by the expression of AMP-activated protein kinase (AMPK) and tissue inhibitor of metalloproteinase 4 (TIMP4). Alizarin red S staining was used to measure calcium deposition. Studies were carried out in VSMCs. Results Zingerone induced the expression of 2 markers of VSMCs differentiation (α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)) and decreased the expression of core-binding factor α-1 (CBFA1). Additionally, zingerone decreased inorganic phosphate (Pi)-induced expression of distal-less homeobox 5 and CBFA1. AMPK phosphorylation and TIMP4 expression were increased by zingerone. Importantly, zingerone protected VSMCs from calcification, and this protective effect was confirmed by increased TIMP4 via overexpression of AMPK, and inhibition of TIMP4 by Compound C. Zingerone upregulated AMPK/TIMP4 expression and recovered Pi-induced inhibition of TIMP4. Conclusions Taken together, our results show that zingerone inhibits Pi-induced vascular calcification by regulating the AMPK/TIMP4 signaling cascade in VSMCs. These results suggest that the natural product zingerone could be useful for treating vascular and metabolic diseases.
#Zingerone #AMP-activated protein kinase #Tissue inhibitor of metalloproteinase-4

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References (36)

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Surh Y / 1999 / Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances / Mutat Res 428:305~327 google schola Daily JW / 2015 / Efficacy of ginger for alleviating the symptoms of primary dysmenorrhea : a systematic review and meta-analysis of randomized clinical trials / Pain Med 16:2243~2255 google schola Ali BH / 2008 / Some phytochemical, pharmacological and toxicological properties of ginger(Zingiber officinale Roscoe) : a review of recent research / Food Chem Toxicol 46:409~420 google schola Chen JC / 2007 / Ginger and its bioactive component inhibit enterotoxigenic Escherichia coli heat-labile enterotoxin-induced diarrhea in mice / J Agric Food Chem 55:8390~8397 google schola Bae WY / 2016 / Zingerone suppresses angiogenesis via inhibition of matrix metalloproteinases during tumor development / Oncotarget 7:47232~47241 google schola

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