PMID- 37569348 OWN - NLM STAT- MEDLINE DCOM- 20230814 LR - 20230814 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 15 DP - 2023 Jul 26 TI - Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Ctheta-Mediated IL-4/STAT6 Signaling Pathway. LID - 10.3390/ijms241511970 [doi] LID - 11970 AB - Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCtheta) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCtheta and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-kappaB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCtheta and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma. FAU - Song, Yu Na AU - Song YN AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. AD - Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea. FAU - Lee, Jae-Won AU - Lee JW AUID- ORCID: 0000-0003-0438-6732 AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. FAU - Ryu, Hyung Won AU - Ryu HW AUID- ORCID: 0000-0001-5291-3942 AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. FAU - Lee, Jae Kyoung AU - Lee JK AD - Rpbio Research Institute, Rpbio Co., Ltd., Suwon 16229, Republic of Korea. FAU - Oh, Eun Sol AU - Oh ES AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. AD - Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea. FAU - Kim, Doo-Young AU - Kim DY AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. FAU - Ro, Hyunju AU - Ro H AD - Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea. FAU - Yoon, Dahye AU - Yoon D AUID- ORCID: 0000-0002-0286-8896 AD - Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Republic of Korea. FAU - Park, Ji-Yoon AU - Park JY AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. AD - Department of Anatomy & Cell Biology, Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea. FAU - Hong, Sung-Tae AU - Hong ST AUID- ORCID: 0000-0001-5981-4859 AD - Department of Anatomy & Cell Biology, Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea. FAU - Kim, Mun-Ock AU - Kim MO AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. FAU - Lee, Su Ui AU - Lee SU AUID- ORCID: 0000-0002-6455-5414 AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea. FAU - Lee, Dae Young AU - Lee DY AUID- ORCID: 0000-0003-4302-3096 AD - Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Republic of Korea. LA - eng GR - Project No. PJ01601601, PJ01601602/Rural Development Administration/ PT - Journal Article DEP - 20230726 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Asthmatic Agents) RN - 207137-56-2 (Interleukin-4) RN - 0 (Cytokines) RN - 37341-29-0 (Immunoglobulin E) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Mice MH - *Anti-Asthmatic Agents/pharmacology/therapeutic use MH - Interleukin-4/metabolism MH - *Asthma/metabolism MH - Lung/metabolism MH - Cytokines/metabolism MH - *Hypersensitivity/metabolism MH - Signal Transduction MH - Inflammation/metabolism MH - Immunoglobulin E MH - *Panax/metabolism MH - Ovalbumin MH - Mice, Inbred BALB C MH - Disease Models, Animal PMC - PMC10418634 OTO - NOTNLM OT - PKCtheta OT - STAT6 OT - Th2 cytokines OT - asthma OT - black ginseng extract COIS- The authors declare no conflict of interest. EDAT- 2023/08/12 10:49 MHDA- 2023/08/14 06:42 PMCR- 2023/07/26 CRDT- 2023/08/12 01:08 PHST- 2023/07/07 00:00 [received] PHST- 2023/07/24 00:00 [revised] PHST- 2023/07/25 00:00 [accepted] PHST- 2023/08/14 06:42 [medline] PHST- 2023/08/12 10:49 [pubmed] PHST- 2023/08/12 01:08 [entrez] PHST- 2023/07/26 00:00 [pmc-release] AID - ijms241511970 [pii] AID - ijms-24-11970 [pii] AID - 10.3390/ijms241511970 [doi] PST - epublish SO - Int J Mol Sci. 2023 Jul 26;24(15):11970. doi: 10.3390/ijms241511970.