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Research articles

ScienceAsia 51 (2023): 1-10 |doi: 10.2306/scienceasia1513-1874.2023.048


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


Fuling Cena,b, Yanmei Weib, Xuan Zhangb, Hanmeng Liub, Guangying Chena,b,*

 
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.

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a College of pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350000 China
b Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158 China

* Corresponding author, E-mail: chgying123@163.com

Received 7 Jan 2025, Accepted 2 May 2025