PMID- 38538755 OWN - NLM STAT- MEDLINE DCOM- 20240429 LR - 20240429 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 73 IP - 5 DP - 2024 May TI - Bakuchicin alleviates ovalbumin-induced allergic asthma by regulating M2 macrophage polarization. PG - 725-737 LID - 10.1007/s00011-024-01859-8 [doi] AB - OBJECTIVE: Asthma is an airway inflammatory disease caused by activation of numerous immune cells including macrophages. Bakuchicin (BKC) is known to exhibit anti-inflammatory effects and type 2 T helper (Th2) regulation, but has not been investigated for airway inflammation. This study aimed to evaluate the effects of BKC on airway inflammation and demonstrate the mechanisms of macrophage polarization. METHODS: The anti-inflammatory effects were determined using lipopolysaccharide (LPS)-stimulated macrophages. The ovalbumin (OVA)-induced asthma mouse model was used to evaluate the effects of BKC on airway inflammation and Th2 responses. Moreover, the effect of BKC on macrophage polarization was confirmed in bone marrow-derived macrophages (BMDMs) differentiation. RESULTS: BKC suppressed nitric oxide production and expression of pro-inflammatory cytokines by inhibiting signaling pathway in LPS-stimulated macrophages. In an OVA-induced asthma model, BKC treatment alleviated histological changes and mast cell infiltration and reduced the levels of eosinophil peroxidase, beta-hexosaminidase, and immunoglobulin levels. In addition, BKC alleviated Th2 responses and M2 macrophage populations in bronchoalveolar fluid. In BMDMs, BKC suppressed IL-4-induced M2 macrophage polarization and the expression of M2 markers such as arginase-1 and Fizz-1 through inhibiting sirtuin 2 levels. CONCLUSION: BKC could be a drug candidate for the treatment of allergic asthma. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Kim, Yeon-Yong AU - Kim YY AD - Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea. AD - Cell and Matrix Research Institute, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. FAU - Jeong, Seungwon AU - Jeong S AD - Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea. FAU - Lee, Seung Woong AU - Lee SW AD - Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea. FAU - Lee, Seung-Jae AU - Lee SJ AD - Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea. FAU - Rho, Mun-Chual AU - Rho MC AD - Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea. FAU - Kim, Sang-Hyun AU - Kim SH AD - Cell and Matrix Research Institute, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. shkim72@knu.ac.kr. FAU - Lee, Soyoung AU - Lee S AD - Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea. sylee@kribb.re.kr. LA - eng GR - KGM5242322/KRIBB Research Initiative Program/ GR - 2022M3A9G8082645/National Research Foundation of Korea grants/ PT - Journal Article DEP - 20240327 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 9006-59-1 (Ovalbumin) RN - 0 (Cytokines) RN - 31C4KY9ESH (Nitric Oxide) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Lipopolysaccharides) SB - IM MH - Animals MH - *Asthma/drug therapy/chemically induced/immunology MH - *Ovalbumin MH - *Macrophages/drug effects/immunology MH - Mice MH - *Mice, Inbred BALB C MH - Female MH - Cytokines/metabolism MH - Nitric Oxide/metabolism MH - Bronchoalveolar Lavage Fluid/cytology/immunology MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Th2 Cells/immunology/drug effects MH - Lipopolysaccharides MH - Lung/pathology/drug effects/immunology MH - Mice, Inbred C57BL OTO - NOTNLM OT - Airway inflammation OT - Bakuchicin OT - Macrophage polarization OT - Macrophages OT - Sirtuin 2 EDAT- 2024/03/28 06:45 MHDA- 2024/04/29 13:58 CRDT- 2024/03/28 00:27 PHST- 2023/11/08 00:00 [received] PHST- 2024/02/02 00:00 [accepted] PHST- 2023/12/20 00:00 [revised] PHST- 2024/04/29 13:58 [medline] PHST- 2024/03/28 06:45 [pubmed] PHST- 2024/03/28 00:27 [entrez] AID - 10.1007/s00011-024-01859-8 [pii] AID - 10.1007/s00011-024-01859-8 [doi] PST - ppublish SO - Inflamm Res. 2024 May;73(5):725-737. doi: 10.1007/s00011-024-01859-8. Epub 2024 Mar 27.