PMID- 34818666 OWN - NLM STAT- MEDLINE DCOM- 20220221 LR - 20221214 IS - 1738-8872 (Electronic) IS - 1017-7825 (Print) IS - 1017-7825 (Linking) VI - 32 IP - 1 DP - 2022 Jan 28 TI - Effects of 3'-isovaleryl-4'-senecioylkhellactone from Peucedanum japonicum Thunberg on PMA-Stimulated Inflammatory Response in A549 Human Lung Epithelial Cells. PG - 81-90 LID - 10.4014/jmb.2107.07001 [doi] AB - 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-1beta. Additionally, it inhibited the phosphorylation of IkappaB kinase (IKK), p65, Ikappa-Balpha, 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-kappaB (NF-kappaB) 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-kappaB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases. FAU - Hwang, Daseul AU - Hwang D AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. AD - College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea. FAU - Ryu, Hyung Won AU - Ryu HW AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. FAU - Park, Ji-Won AU - Park JW AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. FAU - Kim, Jung-Hee AU - Kim JH AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. FAU - Kim, Doo-Young AU - Kim DY AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. FAU - Oh, Jae-Hoon AU - Oh JH AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. AD - College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea. FAU - Kwon, Ok-Kyoung AU - Kwon OK AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. FAU - Han, Sang-Bae AU - Han SB AD - College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea. FAU - Ahn, Kyung-Seop AU - Ahn KS AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea. LA - eng PT - Journal Article PL - Korea (South) TA - J Microbiol Biotechnol JT - Journal of microbiology and biotechnology JID - 9431852 RN - 0 (Anti-Inflammatory Agents) RN - 0 (CXCL8 protein, human) RN - 0 (Cytokines) RN - 0 (IL1B protein, human) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-8) RN - 0 (Phorbol Esters) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor AP-1) RN - 20839-06-9 (phorbol-12-myristate) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - A549 Cells/drug effects MH - Anti-Inflammatory Agents/*pharmacology MH - Apiaceae/*metabolism MH - Cytokines/metabolism MH - Epithelial Cells/*drug effects MH - Humans MH - I-kappa B Kinase/metabolism MH - Inflammation MH - Inflammation Mediators/metabolism MH - Interleukin-1beta MH - Interleukin-8 MH - Lung/*drug effects MH - Mitogen-Activated Protein Kinases/metabolism MH - Phorbol Esters/*pharmacology MH - RNA, Messenger/metabolism MH - Transcription Factor AP-1/metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC9628833 OTO - NOTNLM OT - 3'-isovaleryl-4'-senecioylkhellactone OT - AP-1 OT - NF-kappaB OT - Peucedanum japonicum Thunberg OT - inflammation COIS- Conflict of Interest The authors have no financial conflicts of interest to declare. EDAT- 2021/11/25 06:00 MHDA- 2022/02/22 06:00 PMCR- 2021/11/14 CRDT- 2021/11/24 20:10 PHST- 2021/07/02 00:00 [received] PHST- 2021/11/10 00:00 [revised] PHST- 2021/11/12 00:00 [accepted] PHST- 2021/11/25 06:00 [pubmed] PHST- 2022/02/22 06:00 [medline] PHST- 2021/11/24 20:10 [entrez] PHST- 2021/11/14 00:00 [pmc-release] AID - jmb.2107.07001 [pii] AID - jmb-32-1-81 [pii] AID - 10.4014/jmb.2107.07001 [doi] PST - ppublish SO - J Microbiol Biotechnol. 2022 Jan 28;32(1):81-90. doi: 10.4014/jmb.2107.07001.