Scientific Reports
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2017
·Vol. 7
·期 1
·1-13
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IF 4.259
Zhao Wenwen,Feng Haitao,Guo Shuhui,Han Yantao,Chen Xiuping
ICAM-1 overexpression and subsequent adhesion of leukocytes to endothelial cells play critical roles in the early stage of atherosclerosis. Danshenol A (DA) is an abietane-type diterpenoid isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. The mechanisms under its regulation of adhesion of molecular expression are explored. Here, the effect of DA on TNF-α-induced ICAM-1 expression was investigated in endothelial cells. TNF-α-induced ICAM-1 expression and subsequent adhesion of monocytes, as well as elevated reactive oxygen species (ROS) generation and NOX4 expression were all significantly reversed by DA, siNOX4 and NOX4 inhibitor GKT137831. Furthermore, TNF-α-induced ICAM-1 expression, which was increased via IKKβ/IκBα-mediated activation of NF-κB p65, was also inhibited by DA. Interestingly, NOX4 overexpression suppressed the ICAM-1 expression, and this finding may be ascribed to the activation of Nrf-2. Additionally, NF-κB inhibitor PDTC, siNOX4, or DA can decrease the TNF-α-induced ICAM-1 expression and suppress the adhesion of monocytes. In all, DA inhibited TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion to endothelial cells through the NOX4-dependent IKKβ/NF-κB pathway. Besides, NOX4 played dual role in regulating ICAM-1 expression via diverse signal pathway. This novel bioactivity will make DA a good candidate to be further explored for therapeutic or preventive application for atherosclerosis.
研究领域:
药理学
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心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Endocrine Metabolic & Immune Disorders-Drug Targets
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2025
·Vol. 26
·期 1
·E18715303382831
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IF 2
Yuting Chen,Jie Min,Xiali Yu,Haixiang Ni,Yamei Jin
IntroductionAn increase in the intraorbital adipose tissue is the main pathological feature of thyroid-associated ophthalmopathy (TAO). IGF-1R activates PI3K/AKT signaling and accelerates adipogenesis. Pingmu decoction has been demonstrated to promote orbital adipocyte apoptosis; however, less is reported regarding the action mechanism of Danshenol A (DA), a single active ingredient of Salvia miltiorrhiza (Danshen). Accordingly, this study aimed to investigate the role and association of DA and IGF-1R in the proliferation and lipid accumulation of orbital adipocytes.MethodsPrimary human orbital preadipocytes were chosen and authenticated using immunofluorescence. Cells were treated with the IGF-1R agonist ginsenoside Rg5, IGF-1R overexpression plasmid, dexamethasone (Dex), and/or DA, after which cell proliferation and differentiation were assessed by cell counting kit-8 (CCK-8), oil red O staining, real-time quantitative polymerase chain reaction, and Western blot assays.ResultsOrbital preadipocytes showed positive expression of Pref-1. Treatment with IGF-1R agonist, as well as Dex, promoted orbital adipocyte viability and lipid accumulation, and increased the expression of adiponectin and leptin. It was observed that the overexpression of IGF-1R boosted PI3K/AKT activation and elevated PPARγ and C/EBPα expressions. Importantly, DA reversed the effects of IGF-1R on cell viability, lipid accumulation, and the PI3K/AKT signaling pathway.DiscussionThis study, for the first time, revealed the molecular mechanism by which DA regulates orbital fat metabolism through targeted inhibition of the IGF-1R/PI3K/AKT signaling axis. Notably, IGF-1R overexpression partially counteracted the inhibitory effect of DA, suggesting that this component has multi-target regulatory characteristics.ConclusionThis study not only reveals a new mechanism by which DA treats TAO but also provides theoretical support for the treatment of adipose metabolism.
研究领域:
内分泌学
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眼科学
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分子生物学
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信号转导
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脂肪代谢
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中药药理学
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DOI
PubMed
高影响因子
Food Bioscience
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2023
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IF 5.2
Jiangnan Hu,Lina Shi,Lei Zhu,Xinmei Sha,Yue Li,Junrui Ma,Qing Zhang,Rui Yang
Ferritin is a universal macromolecule protein that stores iron and regulates iron oxidative deposition and release. The physicochemical properties of ferritin can be affected by coexisting bioactive substances. This study investigated the effects of two phenolic acid analogs (caffeic acid and tanshinol) on the physicochemical properties of soybean ferritin. The results indicated that Fe(III) interacted with caffeic acid or tanshinol to form phenolic acid-Fe(III) complexes, and interacted with ferritin to form a ferritin-phenolic acid-Fe(III) complex with hydrogen bonds , which affected the ferritin structure of the complexes to a different extent due to their different structures. Caffeic acid and tanshinol facilitated iron oxidative deposition and release by promoting the Fe(II)-oxidation reaction and increasing Fe(III)-release from ferritin, while caffeic acid exhibited a more pronounced effect. In addition, caffeic acid protected ferritin from degradation by free radicals during the release of iron. Caffeic acid displayed a higher Fe(II) chelating ability and a higher hydroxyl radical ( • OH) scavenging ability owing to the conjugated structure compared to tanshinol. These findings elucidated the mechanism for the interaction among ferritin, iron, and polyphenols, and provide a theoretical basis for applying ferritin in protein-ligand interactions and iron supplementation of food .
研究领域:
生物化学
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食品科学
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蛋白质化学
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DOI
高影响因子
危险品化学品经营许可证（带存储）