{"title":"<i>p</i>-Coumaric acid modulates cholesterol efflux and lipid accumulation and inflammation in foam cells.","authors":"Ha-Rin Moon, Jung-Mi Yun","doi":"10.4162/nrp.2024.18.6.774","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong>Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The <i>p</i>-coumaric acid (<i>p-</i>CA) contained in vegetables may have various physiological activities. The inhibitory effect of <i>p</i>-CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of <i>p</i>-CA on foam cells by co-treatment with oxidized low-density lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis <i>in vitro</i> and studied the regulation of its underlying mechanisms.</p><p><strong>Materials/methods: </strong>THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of <i>p</i>-CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA.</p><p><strong>Results: </strong>Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, <i>p</i>-CA treatment inhibited lipid accumulation. <i>p</i>-CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, <i>p</i>-CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. <i>p</i>-CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6.</p><p><strong>Conclusion: </strong><i>p</i>-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.</p>","PeriodicalId":19232,"journal":{"name":"Nutrition Research and Practice","volume":"18 6","pages":"774-792"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621437/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition Research and Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4162/nrp.2024.18.6.774","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
p-Coumaric acid modulates cholesterol efflux and lipid accumulation and inflammation in foam cells.
Background/objectives: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The p-coumaric acid (p-CA) contained in vegetables may have various physiological activities. The inhibitory effect of p-CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of p-CA on foam cells by co-treatment with oxidized low-density lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis in vitro and studied the regulation of its underlying mechanisms.
Materials/methods: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of p-CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA.
Results: Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, p-CA treatment inhibited lipid accumulation. p-CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, p-CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. p-CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6.
Conclusion: p-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.
期刊介绍:
Nutrition Research and Practice (NRP) is an official journal, jointly published by the Korean Nutrition Society and the Korean Society of Community Nutrition since 2007. The journal had been published quarterly at the initial stage and has been published bimonthly since 2010.
NRP aims to stimulate research and practice across diverse areas of human nutrition. The Journal publishes peer-reviewed original manuscripts on nutrition biochemistry and metabolism, community nutrition, nutrition and disease management, nutritional epidemiology, nutrition education, foodservice management in the following categories: Original Research Articles, Notes, Communications, and Reviews. Reviews will be received by the invitation of the editors only. Statements made and opinions expressed in the manuscripts published in this Journal represent the views of authors and do not necessarily reflect the opinion of the Societies.