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单体和二聚体芪类化合物对骨髓来源树突状细胞中细菌诱导细胞因子和 LPS 诱导 ROS 形成的影响的研究。

Investigation of the Effects of Monomeric and Dimeric Stilbenoids on Bacteria-Induced Cytokines and LPS-Induced ROS Formation in Bone Marrow-Derived Dendritic Cells.

机构信息

Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1871 Frederiksberg, Denmark.

Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy.

出版信息

Int J Mol Sci. 2023 Feb 1;24(3):2731. doi: 10.3390/ijms24032731.

Abstract

Stilbenoids are anti-inflammatory and antioxidant compounds, with resveratrol being the most investigated molecule in this class. However, the actions of most other stilbenoids are much less studied. This study compares five monomeric (resveratrol, piceatannol, pterostilbene, pinostilbene, and trimethoxy-resveratrol) and two dimeric (dehydro-δ-viniferin and -δ-viniferin) stilbenoids for their capability to modulate the production of bacteria-induced cytokines (IL-12, IL-10, and TNF-α), as well as lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), in murine bone marrow-derived dendritic cells. All monomeric species showed dose-dependent inhibition of -induced IL-12 and TNF-α, whereas only resveratrol and piceatannol inhibited IL-10 production. All monomers, except trimethoxy-resveratrol, inhibited -induced IL-12, IL-10, and TNF-α production. The dimer dehydro-δ-viniferin remarkably enhanced -induced IL-12 production. The contrasting effect of resveratrol and dehydro-δ-viniferin on IL-12 production was due, at least in part, to a divergent inactivation of the mitogen-activated protein kinases by the two stilbenoids. Despite having moderate to high total antioxidant activity, dehydro-δ-viniferin was a weak inhibitor of LPS-induced ROS formation. Conversely, resveratrol and piceatannol potently inhibited LPS-induced ROS formation. Methylated monomers showed a decreased antioxidant capacity compared to resveratrol, also depending on the methylation site. In summary, the immune-modulating effect of the stilbenoids depends on both specific structural features of tested compounds and the stimulating bacteria.

摘要

芪类化合物具有抗炎和抗氧化作用,白藜芦醇是该类化合物中研究最多的分子。然而,大多数其他芪类化合物的作用研究得要少得多。本研究比较了五种单体(白藜芦醇、白皮杉醇、紫檀芪、根皮素和三甲氧基白藜芦醇)和两种二聚体(去氢-δ-viniferin 和 -δ-viniferin)芪类化合物调节细菌诱导细胞因子(IL-12、IL-10 和 TNF-α)产生的能力,以及脂多糖(LPS)诱导的活性氧(ROS)在鼠骨髓来源树突状细胞中的作用。所有单体均表现出剂量依赖性抑制 - 诱导的 IL-12 和 TNF-α,而只有白藜芦醇和白皮杉醇抑制 IL-10 产生。除三甲氧基白藜芦醇外,所有单体均抑制 - 诱导的 IL-12、IL-10 和 TNF-α 产生。二聚体去氢-δ-viniferin 显著增强了 - 诱导的 IL-12 产生。白藜芦醇和去氢-δ-viniferin 对 IL-12 产生的相反作用至少部分归因于两种芪类化合物对丝裂原活化蛋白激酶的不同失活作用。尽管具有中等至高的总抗氧化活性,但去氢-δ-viniferin 是 LPS 诱导 ROS 形成的弱抑制剂。相反,白藜芦醇和白皮杉醇强烈抑制 LPS 诱导的 ROS 形成。与白藜芦醇相比,甲基化单体的抗氧化能力降低,这也取决于甲基化部位。总之,芪类化合物的免疫调节作用取决于所测试化合物的特定结构特征和刺激细菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65df/9917081/594680604cdf/ijms-24-02731-g001.jpg

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