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Effects of 3'-isovaleryl-4'-senecioylkhellactone from Peucedanum japonicum Thunberg on PMA-Stimulated Inflammatory Response in A549 Human Lung Epithelial Cells

  • Hwang, Daseul (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ryu, Hyung Won (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Ji-Won (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Jung-Hee (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Doo-Young (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Jae-Hoon (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kwon, Ok-Kyoung (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Han, Sang-Bae (College of Pharmacy, Chungbuk National University) ;
  • Ahn, Kyung-Seop (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2021.07.02
  • Accepted : 2021.11.12
  • Published : 2022.01.28

Abstract

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.

Keywords

Acknowledgement

The authors thank the Won HJ (current address: Natural Product Research Center, Korea Institute of Science & Technology, Gangneung 25451, Republic of Korea) for providing the IVSK. This work was supported by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM5522211) and the Ministry of Health and Welfare (HI14C1277) of Republic of Korea.

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