Toxicological Research

  • 제41권1호
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  • Pages.47-59
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  • 2025
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지
DOI QR코드

DOI QR Code

Rocaglamide-A mitigates LPS-induced hepatic inflammation by modulating JNK/AP-1 signaling cascade and ROS production in hepatocytes

  • Yoon-su Ha (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Taek-Kyong Kim (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Jun Heo (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Jintaek Oh (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Seung-Kyoon Kim (Department of Convergent Bioscience and Informatics, College of Bioscience and Biotechnology, Chungnam National University) ;
  • Jeongkyu Kim (Department of Life Science, Chung-Ang University) ;
  • Jeonghyung Lee (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Se-Ran Yang (Global/Gangwon Innovative Biologics-Regional Leading Research Center (GIB-RLRC), Kangwon National University) ;
  • Seonghwan Hwang (College of Pharmacy and Research Institute for Drug Development, Pusan National University) ;
  • Seung-Jin Kim (Department of Biochemistry, College of Natural Sciences, Kangwon National University)
  • 투고 : 2024.06.04
  • 심사 : 2024.09.10
  • 발행 : 2025.01.15
⟨ 이전 논문 다음 논문 ⟩

초록

Lipopolysaccharide (LPS), a gut-derived endotoxin, is a recognized risk factor for both Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Rocaglamide-A (Roc-A), a natural compound derived from the genus Aglaia, is known for its pharmacological and immunosuppressive effects on various cell types. Although our recent investigations have unveiled Roc-A's anti-adipogenic role in adipocytes, its mechanism in hepatic inflammation remains elusive. This study delves into Roc-A's protective effects on LPS-induced hepatic inflammation. Our results demonstrated that Roc-A treatment significantly reduced the LPS-induced production of inflammatory cytokines in hepatocytes. Intriguingly, Roc-A decreased LPS-induced production of reactive oxygen species (ROS), upregulated antioxidant gene expression, and downregulated endoplasmic reticulum (ER) stress-related gene expression. Mechanistically, Roc-A significantly attenuated LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1). Notably, this effect was abolished by the JNK activator Anisomycin, while the JNK inhibitor SP600125 enhanced it. Furthermore, Roc-A suppressed the expression of NF-κB target genes, including inducible nitric oxide synthase (iNOS), thereby alleviating iNOS-derived nitric oxide (NO) production. These findings collectively indicate that Roc-A has the potential to alleviate LPS-induced nitrosative/oxidative stress and hepatic inflammation by inhibiting JNK phosphorylation. Thus, Roc-A emerges as a promising anti-inflammatory intervention for LPS-induced hepatic inflammation.

키워드

과제정보

The authors thank Dr. Young-Myeong Kim for sharing materials and technical assistance for this study. The graphical image was partly generated using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com.

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