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红藻次生代谢产物对MAPK/NF-κB信号通路和NLRP3炎性小体的调控:一项机制研究

Modulation of MAPK/NF-κB Pathway and NLRP3 Inflammasome by Secondary Metabolites from Red Algae: A Mechanistic Study.

作者信息

Nabil-Adam Asmaa, Ashour Mohamed L, Shreadah Mohamed Attia

机构信息

Marine Biotechnology and Natural Products Laboratory, National Institute of Oceanography & Fisheries, Alexandria 21556, Egypt.

Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Abbasia, Cairo 11566, Egypt.

出版信息

ACS Omega. 2023 Oct 5;8(41):37971-37990. doi: 10.1021/acsomega.3c03480. eCollection 2023 Oct 17.

DOI:10.1021/acsomega.3c03480
PMID:37867644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10586274/
Abstract

The pharmacological properties of seaweeds are diverse. No studies have been conducted on the protective effect of (GOE) against lippopolysaccharide (LPS)-induced inflammation in the brain. This study is divided into three phases, the first of which is the initial phase. In vitro study includes antioxidant, radical scavenging, and anti-inflammatory activities, including cyclooxygenase-1 (COX1), COX2, NO, acetylcholine inhibition, sphingosine kinase 1, tumor necrosis factor α (TNF-α), and interleukin-6, as well as antioxidant and radical-scavenging activities, including 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid. Using LPS-induced acute inflammation, the second phase was conducted in vivo. Antioxidant and anti-inflammatory assays were performed to investigate the protective role of GOE. In addition to the phytochemical analysis, the bioactive content of GOE was also investigated. In vitro results demonstrated the potential of GOE as an antioxidant, anti-inflammatory, and neuroprotective agent. A study using LPS as an induced lung injury and neuroinflammation model confirmed the in vitro results. The GOE significantly reduced inflammatory, oxidative, and neurodegenerative biomarkers based on histopathological and immuno-histochemistry results. Based on computational drug design, four target proteins were approved: nuclear factor κB, mitogen-activated protein kinases, TNF-α, and NLRP3. Using polyphenolic compounds in GOE as ligands demonstrated good alignment and affinity against the three proteins. Finally, the current study offers a new approach to developing drug leads considering GOE's protective and curative roles.

摘要

海藻的药理特性多种多样。尚未有关于甘油醚提取物(GOE)对脂多糖(LPS)诱导的脑部炎症的保护作用的研究。本研究分为三个阶段,第一阶段为初始阶段。体外研究包括抗氧化、自由基清除和抗炎活性,涉及环氧合酶-1(COX1)、COX2、一氧化氮、乙酰胆碱抑制、鞘氨醇激酶1、肿瘤坏死因子α(TNF-α)和白细胞介素-6,以及抗氧化和自由基清除活性,包括2,2-二苯基-1-苦基肼和2,2'-偶氮双(3-乙基苯并噻唑啉)-6-磺酸。利用LPS诱导的急性炎症,在体内进行了第二阶段研究。进行抗氧化和抗炎试验以研究GOE的保护作用。除了植物化学分析外,还研究了GOE的生物活性成分。体外研究结果表明GOE具有作为抗氧化、抗炎和神经保护剂的潜力。一项以LPS作为诱导肺损伤和神经炎症模型的研究证实了体外研究结果。基于组织病理学和免疫组织化学结果,GOE显著降低了炎症、氧化和神经退行性生物标志物。基于计算药物设计,确定了四种靶蛋白:核因子κB、丝裂原活化蛋白激酶、TNF-α和NLRP3。使用GOE中的多酚化合物作为配体,显示出与这三种蛋白具有良好的匹配度和亲和力。最后,考虑到GOE的保护和治疗作用,本研究为开发药物先导物提供了一种新方法。

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