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碳量子点通过抑制脑出血后NLRP3炎性小体放大表没食子儿茶素没食子酸酯对神经损伤的有益作用。

Carbon quantum dots amplify beneficial effects of EGCG against neural injuries by NLRP3 inflammasome after intracerebral hemorrhage.

作者信息

Xiao Min, Pan Yun, Tang Shijin, Guo Tingwang, Yang Lin, Chen Gang

机构信息

School of Food Science and Engineering, Chongqing Technology and Business University, Chongqing 400067, China.

Department of Gastroenterology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.

出版信息

Int J Pharm. 2025 Feb 25;671:125281. doi: 10.1016/j.ijpharm.2025.125281. Epub 2025 Jan 26.

Abstract

Neuroinflammation plays an indispensable role in neural damages after ICH, responsible for the induced high mortality and poor prognosis. NLRP3 inflammasome, which is known mediated by ROS, has been widely documented to aggravate brain injuries. Therefore, suppressing neural injuries by ROS/NLRP3 pathway may be beneficial in treating ICH. As the major catechin found in green tea, epigallocatechin-3-gallate (EGCG) shows excellent anti-oxidative and anti-inflammatory effects. In this study, EGCG-carbon quantum dots (EGCG-CQDs) were successfully fabricated based on EGCG by hydrothermal synthesis method. EGCG-CQDs exhibited an excellent aqueous solubility, and emerged more abundant phenolic oxygens as well as oxygen-rich functional groups. Importantly, EGCG-CQDs showed superior free radical scavenging activity by DPPH and ABTS assays in vitro than EGCG. In vivo, a significant antioxidative activity was presented by EGCG-CQDs rather than EGCG. Furthermore, the upregulated NLRP3 and the induced inflammatory cascades (NF-κB, Caspase-1 and GSDMD) in ICH were attenuated by EGCG-CQDs. Inflammatory factor productions were also decreased by EGCG-CQDs, such as IL-1β, IL-18, IL-6 and TNF-α. Finally, the disturbed neural viability, disordered cytomorphology, and neurological deficits were significantly improved by EGCG-CQDs rather than EGCG. Therefore, CQDs might be an effective form to amplify the efficacy and bioavailability of EGCG, exerting considerable effects on treating ICH by suppressing ROS/NLRP3.

摘要

神经炎症在脑出血后的神经损伤中起着不可或缺的作用,是导致高死亡率和不良预后的原因。已知由活性氧介导的NLRP3炎性小体已被广泛证明会加重脑损伤。因此,通过活性氧/NLRP3途径抑制神经损伤可能对治疗脑出血有益。作为绿茶中发现的主要儿茶素,表没食子儿茶素-3-没食子酸酯(EGCG)具有出色的抗氧化和抗炎作用。在本研究中,通过水热合成法成功制备了基于EGCG的EGCG-碳量子点(EGCG-CQDs)。EGCG-CQDs表现出优异的水溶性,并出现了更丰富的酚氧基以及富含氧的官能团。重要的是,通过体外DPPH和ABTS测定,EGCG-CQDs显示出比EGCG更强的自由基清除活性。在体内,EGCG-CQDs而非EGCG表现出显著的抗氧化活性。此外,EGCG-CQDs减轻了脑出血中上调的NLRP3以及诱导的炎症级联反应(NF-κB、半胱天冬酶-1和GSDMD)。EGCG-CQDs还降低了炎症因子的产生,如IL-1β、IL-18、IL-6和TNF-α。最后,EGCG-CQDs而非EGCG显著改善了受损的神经活力、紊乱的细胞形态和神经功能缺损。因此,碳量子点可能是增强EGCG疗效和生物利用度的有效形式,通过抑制活性氧/NLRP3对治疗脑出血发挥显著作用。

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