AS-1 attenuates the inflammatory response by targeting AKT and MAPK in LPS-activated acute lung injury models

IF 0.9 4区 综合性期刊 Q3 MULTIDISCIPLINARY SCIENCES
Fuling Cen, Yan-Mei Wei, Xuan Zhang, Hanmeng Liu, Guang‐Ying Chen
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Abstract

We investigated the effects of 3,28-dihydroxyolean-12-ene (AS-1) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in Balb/c mice and attempted to elucidate its underlying mechanism of action.The levels of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and interleukin-1 (IL-1) were measured using an ELISA kit.Furthermore, we analyzed the protein expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the proteins involved in the kinase B/mitogen-activated protein kinase (AKT/MAPK) signaling pathways by Western blot analysis.Additionally, we evaluated AS-1 for toxicity and teratogenicity using the Cell Counting Kit-8 (CCK-8) assay and the zebrafish embryo toxicity assay.The results revealed that AS-1 suppressed the expression of pro-inflammatory cytokines and the phosphorylation of MAPK-related proteins, while enhancing the phosphorylation of AKT-related proteins.Furthermore, AS-1 was found to be non-teratogenic at concentrations below 12.5 M.These findings suggest that AS-1 may alleviate ALI by modulating the AKT/MAPK signaling pathway.
在lps激活的急性肺损伤模型中,AS-1通过靶向AKT和MAPK减轻炎症反应
我们研究了3,28-二羟基齐墩烯-12-烯(AS-1)对脂多糖(LPS)诱导的Balb/c小鼠急性肺损伤(ALI)的影响,并试图阐明其作用机制。采用ELISA试剂盒检测促炎细胞因子如肿瘤坏死因子- (TNF-)、白细胞介素-6 (IL-6)、白细胞介素-1 (IL-1)水平。此外,我们还通过Western blot分析了诱导型一氧化氮合酶(iNOS)、环氧合酶-2 (COX-2)和激酶B/丝裂原活化蛋白激酶(AKT/MAPK)信号通路相关蛋白的表达水平。此外,我们使用细胞计数试剂盒-8 (CCK-8)试验和斑马鱼胚胎毒性试验评估了AS-1的毒性和致畸性。结果显示,AS-1抑制促炎细胞因子的表达和mapk相关蛋白的磷酸化,同时增强akt相关蛋白的磷酸化。此外,在浓度低于12.5 m时发现AS-1无致畸性。这些发现表明,AS-1可能通过调节AKT/MAPK信号通路来缓解ALI。
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来源期刊
Scienceasia
Scienceasia MULTIDISCIPLINARY SCIENCES-
CiteScore
1.70
自引率
33.30%
发文量
102
审稿时长
1 months
期刊介绍: ScienceAsia is a multidisciplinary journal publishing papers of high quality bimonthly, in printed and electronic versions, by the Science Society of Thailand under Royal Patronage and the National Research Council of Thailand. The journal publishes original research papers that provide novel findings and important contribution to broad area in science and mathematics. Areas covered include Biological Sciences and Biotechnology, Chemistry and Material Sciences, Environmental and Applied Sciences, and Mathematics and Physical Sciences. Manuscripts may report scientifically useful data, observations or model predictions, and/or provide a new scientific concept or a new explanation of published results. Submissions of materials of current scientific interest are highly welcome, provided that there is sufficient scientific merit. The journal will not accept manuscripts which have been published or are being considered for publication elsewhere, nor should manuscripts being considered by ScienceAsia be submitted to other journals. Submitted manuscripts must conform to the guidelines given in the Instructions for Authors
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