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新型香芹酚衍生物对3T3-L1和WJ-MSCs细胞的抗肥胖和抗炎作用

Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells.

作者信息

Cacciatore Ivana, Spalletta Sonia, Di Rienzo Annalisa, Flati Vincenzo, Fornasari Erika, Pierdomenico Laura, Del Boccio Piero, Valentinuzzi Silvia, Costantini Erica, Toniato Elena, Martinotti Stefano, Conte Carmela, Di Stefano Antonio, Robuffo Iole

机构信息

Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.

Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.

出版信息

Pharmaceuticals (Basel). 2023 Feb 22;16(3):340. doi: 10.3390/ph16030340.

Abstract

(1) Background: Obesity, a complex metabolic disease resulting from an imbalance between food consumption and energy expenditure, leads to an increase in adipocytes and chronic inflammatory conditions. The aim of this paper was to synthesize a small series of carvacrol derivatives () that are able to reduce both adipogenesis and the inflammatory status often associated with the progression of the obesity disease. (2) Methods: The synthesis of was performed using classical procedures in a solution phase. Biological studies were performed on three cell lines: 3T3-L1, WJ-MSCs, and THP-1. The anti-adipogenic properties of were evaluated using western blotting and densitometric analysis by assessing the expression of obesity-related proteins, such as ChREBP. The anti-inflammatory effect was estimated by measuring the reduction in TNF-α expression in -treated THP-1 cells. (3) Results: -obtained through a direct linkage between the carboxylic moiety of anti-inflammatory drugs (Ibuprofen, Flurbiprofen, and Naproxen) and the hydroxyl group of carvacrol-have an inhibitory effect on the accumulation of lipids in both 3T3-L1 and WJ-MSCs cell cultures and an anti-inflammatory effect by reducing TNF- α levels in THP-1 cells. (4) Conclusions: Considering the physicochemical properties, stability, and biological data, the derivative-obtained by a direct linkage between carvacrol and naproxen-resulted in the best candidate, displaying anti-obesity and anti-inflammatory effects in vitro.

摘要

(1) 背景:肥胖是一种因食物摄入与能量消耗失衡导致的复杂代谢性疾病,会致使脂肪细胞增多以及慢性炎症状态。本文的目的是合成一小系列香芹酚衍生物(),这些衍生物能够减少脂肪生成以及通常与肥胖疾病进展相关的炎症状态。(2) 方法:采用经典的溶液相方法进行的合成。对三种细胞系进行了生物学研究:3T3 - L1、WJ - 间充质干细胞和THP - 1。通过蛋白质免疫印迹法和光密度分析,评估肥胖相关蛋白如ChREBP的表达,以此来评价的抗脂肪生成特性。通过测量经处理的THP - 1细胞中TNF - α表达的降低情况来评估抗炎效果。(3) 结果:通过抗炎药物(布洛芬、氟比洛芬和萘普生)的羧基部分与香芹酚的羟基直接连接得到的,对3T3 - L1和WJ - 间充质干细胞培养物中的脂质积累具有抑制作用,并通过降低THP - 1细胞中的TNF - α水平发挥抗炎作用。(4) 结论:考虑到物理化学性质、稳定性和生物学数据,由香芹酚与萘普生直接连接得到的衍生物是最佳候选物,在体外显示出抗肥胖和抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11aa/10055808/1c4656d7cb8f/pharmaceuticals-16-00340-sch001.jpg

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