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石榴皮鞣花素在THP-1细胞模型中调节与动脉粥样硬化相关的关键过程。

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model.

作者信息

Almowallad Sanaa, Huwait Etimad, Al-Massabi Rehab, Saddeek Salma, Gauthaman Kalamegam, Prola Alexandre

机构信息

Department of Biochemistry, Faculty of Sciences, King Abdul Aziz University, Jeddah 21589, Saudi Arabia.

Cell Culture Unit, King Fahad Medical Research Centre, King Abdul Aziz University, Jeddah 22252, Saudi Arabia.

出版信息

Pharmaceuticals (Basel). 2020 Nov 8;13(11):372. doi: 10.3390/ph13110372.

Abstract

Atherosclerosis may lead to cardiovascular diseases (CVD), which are the primary cause of death globally. In addition to conventional therapeutics for CVD, use of nutraceuticals that prevents cholesterol deposition, reduce existing plaques and hence anti-atherosclerotic effects of nutraceuticals appeared to be promising. As such, in the present study we evaluated the beneficial effects of punicalagin, a phytochemical against an atherosclerotic cell model in vitro. Cytotoxicity assays were examined for 10 µM concentration of punicalagin on THP-1 macrophages. Real-time-polymerase chain reaction (RT-PCR) was used to analyze monocyte chemoattractant protein-1 (MCP-1) and Intercellular adhesion molecule (ICAM-1) expressions. Monocyte migration and cholesterol efflux assays were performed to investigate punicalagin's further impact on the key steps of atherosclerosis. Cytotoxicity assays demonstrated no significant toxicity for punicalagin (10 µM) on THP-1 macrophages. Punicalagin inhibited the IFN-γ-induced overexpression of MCP-1 and ICAM-1 in macrophages by 10 fold and 3.49 fold, respectively, compared to the control. Punicalagin also reduced the MCP-1- mediated migration of monocytes by 28% compared to the control. Percentages of cellular cholesterol efflux were enhanced in presence or absence of IFN-γ by 88% and 84% compared to control with 58 %and 62%, respectively. Punicalagin possesses anti-inflammatory and anti-atherosclerotic effects. Punicalagin also did not exhibit any cytotoxicity and therefore can be considered a safe and potential candidate for the treatment and prevention of atherosclerosis.

摘要

动脉粥样硬化可能导致心血管疾病(CVD),而心血管疾病是全球主要的死亡原因。除了用于心血管疾病的传统疗法外,使用能防止胆固醇沉积、减少现有斑块的营养保健品,因此营养保健品的抗动脉粥样硬化作用似乎很有前景。因此,在本研究中,我们评估了石榴皮素这种植物化学物质对体外动脉粥样硬化细胞模型的有益作用。检测了10μM浓度的石榴皮素对THP-1巨噬细胞的细胞毒性。采用实时聚合酶链反应(RT-PCR)分析单核细胞趋化蛋白-1(MCP-1)和细胞间黏附分子(ICAM-1)的表达。进行单核细胞迁移和胆固醇流出试验,以研究石榴皮素对动脉粥样硬化关键步骤的进一步影响。细胞毒性试验表明,石榴皮素(10μM)对THP-1巨噬细胞无明显毒性。与对照组相比,石榴皮素分别抑制巨噬细胞中IFN-γ诱导的MCP-1和ICAM-1过表达10倍和3.49倍。与对照组相比,石榴皮素还使MCP-1介导的单核细胞迁移减少了28%。在有或没有IFN-γ的情况下,细胞胆固醇流出百分比分别比对照组提高了88%和84%,对照组分别为58%和62%。石榴皮素具有抗炎和抗动脉粥样硬化作用。石榴皮素也未表现出任何细胞毒性,因此可被认为是治疗和预防动脉粥样硬化的安全且有潜力的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e545/7695206/d4c443db6bdb/pharmaceuticals-13-00372-g001.jpg

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