{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:41:04Z","timestamp":1784760064634,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Chamaecyparis obtusa (Siebold &amp; Zucc.) Endl. (C. obtusa) is an evergreen conifer native to temperate regions such as South Korea and Japan, traditionally used for its anti-inflammatory properties. However, the molecular mechanisms underlying the anti-inflammatory effects of C. obtusa bark extracts remain poorly understood. In this study, I compared the biological activities of C. obtusa bark extracts prepared using boiling water (COWB) and 70% ethanol (COEB), and investigated their anti-inflammatory mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. COEB significantly suppressed both mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), along with decreased production of their respective inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2). Additionally, COEB selectively downregulated interleukin (IL)-1\u03b2 expression, without affecting tumor necrosis factor-\u03b1 (TNF-\u03b1), and unexpectedly upregulated IL-6. Notably, COEB did not inhibit the LPS-induced activation of major inflammatory signaling pathways, including mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-\u03baB), and Janus kinase\/signal transducer and activator of transcription (JAK\/STAT). These findings suggest that COEB exerts anti-inflammatory effects by modulating key inflammatory mediators independently of canonical signaling pathways and may offer a novel therapeutic strategy for controlling inflammation.<\/jats:p>","DOI":"10.3390\/plants14152346","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:16:10Z","timestamp":1753805770000},"page":"2346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bark Extracts of Chamaecyparis obtusa (Siebold &amp; Zucc.) Endl. Attenuate LPS-Induced Inflammatory Responses in RAW264.7 Macrophages"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-5395","authenticated-orcid":false,"given":"Bo-Ae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Cosmetics, College of Health and Safety Science, Mokwon University, Daejeon 35349, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-A","family":"Byeon","sequence":"additional","affiliation":[{"name":"Department of Cosmeceutical Science, Kyungsung University, Busan 48434, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ah","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Science, Daegu Haany University, Gyeongbuk 38540, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jin","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Cosmeceutical Science, Kyungsung University, Busan 48434, Republic of Korea"},{"name":"Department of Cosmetic Science, Kyungsung University, Busan 48434, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1600-0765.2006.00896.x","article-title":"Fundamental mechanisms of host immune responses to infection","volume":"41","author":"Azuma","year":"2006","journal-title":"J. Periodontal Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/1744666X.2020.1719833","article-title":"Epidemiology of major chronic inflammatory immune-related skin diseases in 2019","volume":"16","author":"Pezzolo","year":"2020","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/exd.13336","article-title":"Systemic immune mechanisms in atopic dermatitis and psoriasis with implications for treatment","volume":"27","author":"Krueger","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"428","DOI":"10.4168\/aair.2018.10.5.428","article-title":"Autoimmune responses in severe asthma","volume":"10","author":"Mukherjee","year":"2018","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Janssens, S., and Beyaert, R. (2003). Role of Toll-like receptors in pathogen recognition. Clin. Microbiol. Rev., 16.","DOI":"10.1128\/CMR.16.4.637-646.2003"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mazgaeen, L., and Gurung, P. (2020). Recent advances in lipopolysaccharide recognition systems. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020379"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1016\/S0367-326X(00)00181-7","article-title":"Prostaglandins and nitric oxide as molecular targets for anti-inflammatory therapy","volume":"71","author":"Sautebin","year":"2000","journal-title":"Fitoterapia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"627","DOI":"10.14202\/vetworld.2018.627-635","article-title":"The crucial roles of inflammatory mediators in inflammation: A review","volume":"11","author":"Abdulkhaleq","year":"2018","journal-title":"Vet. World"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s10787-021-00813-y","article-title":"Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation","volume":"29","author":"Nailwal","year":"2021","journal-title":"Inflammopharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cell.2010.02.043","article-title":"Anti-inflammatory agents: Present and future","volume":"140","author":"Dinarello","year":"2010","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2147\/IJICMR.S10200","article-title":"Nonsteroidal anti-inflammatory drugs: Prostaglandins, indications, and side effects","volume":"2011","author":"Pountos","year":"2011","journal-title":"Int. J. Interferon Cytokine Mediat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.1301\/nr.2007.dec.S140-S146","article-title":"Inflammatory mechanisms: The molecular basis of inflammation and disease","volume":"65","author":"Libby","year":"2007","journal-title":"Nutr. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nunes, C.d.R., Arantes, M.B., de Faria Pereira, S.M., Da Cruz, L.L., de Souza Passos, M., De Moraes, L.P., Vieira, I.J.C., and de Oliveira, D.B. (2020). Plants as sources of anti-inflammatory agents. Molecules, 25.","DOI":"10.3390\/molecules25163726"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.2174\/092986712800229069","article-title":"Anti-inflammatory agents from plants: Progress and potential","volume":"19","author":"Recio","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1002\/med.20156","article-title":"Recent developments in anti-inflammatory natural products","volume":"29","author":"Gautam","year":"2009","journal-title":"Med. Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"G\u00f3rski, K.M., Kowalczyk, T., Picot, L., Rijo, P., Ghorbanpour, M., and Sitarek, P. (2024). The precious potential of the sacred tree Chamaecyparis obtusa (Siebold & Zucc.) Endl. as a source of secondary metabolites with broad biological applications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052723"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114493","DOI":"10.1016\/j.jep.2021.114493","article-title":"Chamaecyparis obtusa (Siebold & Zucc.) Endl. leaf extracts prevent inflammatory responses via inhibition of the JAK\/STAT axis in RAW264. 7 cells","volume":"282","author":"Kwon","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.jid.2017.11.039","article-title":"Skin wound healing is accelerated by a lipid mixture representing major lipid components of Chamaecyparis obtusa plant extract","volume":"138","author":"Kim","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116598","DOI":"10.1016\/j.jep.2023.116598","article-title":"Pharmacological anti-tumor effects of natural Chamaecyparis obtusa (siebold & zucc.) endl. Leaf extracts on breast cancer","volume":"313","author":"Kwon","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kim, H.-Y., Lee, S.-G., Oh, T.-J., Lim, S.R., Kim, S.-H., Lee, H.J., Kim, Y.-S., and Choi, H.-K. (2015). Antiproliferative and apoptotic activity of chamaecyparis obtusa leaf extract against the HCT116 human colorectal cancer cell line and investigation of the bioactive compound by gas chromatography-mass spectrometry-based metabolomics. Molecules, 20.","DOI":"10.3390\/molecules201018066"},{"key":"ref_21","first-page":"27","article-title":"Evaluation of Whitening and Antibacterial Efficacy using Chamaecyparis Obtusa (Siebold & Zucc.) Endl Root: Focusing on Functional Cosmetic Materials","volume":"18","author":"Park","year":"2024","journal-title":"J. Altern. Anim. Exp."},{"key":"ref_22","first-page":"1496","article-title":"Studies on the antioxidant and whitening effects of Chamaecyparis obtusa extract","volume":"37","author":"Joung","year":"2020","journal-title":"J. Korean Appl. Sci. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/jsfa.3231","article-title":"Antioxidant activity of the ethanolic extract from the bark of Chamaecyparis obtusa var. formosana","volume":"88","author":"Marimuthu","year":"2008","journal-title":"J. Sci. Food Agric."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.fitote.2006.09.026","article-title":"Chemical composition and antimicrobial activity of Chamaecyparis obtusa leaf essential oil","volume":"78","author":"Yang","year":"2007","journal-title":"Fitoterapia"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Eltayeb, L.M.H., Yagi, S., Mohamed, H.M.M., Zengin, G., Shariati, M.A., Rebezov, M., Uba, A.I., and Lorenzo, J.M. (2023). Essential oils composition and biological activity of Chamaecyparis obtusa, Chrysopogon nigritanus and Lavandula coronopifolia grown wild in Sudan. Molecules, 28.","DOI":"10.3390\/molecules28031005"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Khalil, A.S.E., and Lukasiewicz, M. (2024). The optimization of the hot water extraction of the polysaccharide-rich fraction from Agaricus bisporus. Molecules, 29.","DOI":"10.3390\/molecules29194783"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.ijbiomac.2014.08.058","article-title":"Extraction, characterization and in vitro antioxidant activity of polysaccharides from black soybean","volume":"72","author":"Liu","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Vergara-Salinas, J.R., Cuevas-Valenzuela, J., and P\u00e9rez-Correa, J.R. (2015). Pressurized hot water extraction of polyphenols from plant material. Biotechnology of Bioactive Compounds: Sources and Applications, John Wiley & Sons.","DOI":"10.1002\/9781118733103.ch3"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113170","DOI":"10.1016\/j.microc.2025.113170","article-title":"Optimized extraction technique and solvent to enhance the recovery of bioactive polyphenols from Viola canescens Wall. ex Roxb.: A case study using OFAT and chemical characterization using UPLC-PDA, UHPLC-Q-TOF-IMS and GC\u2013MS","volume":"212","author":"Kaundal","year":"2025","journal-title":"Microchem. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.micron.2014.03.012","article-title":"Detection of lipopolysaccharide induced inflammatory responses in RAW264. 7 macrophages using atomic force microscope","volume":"65","author":"Pi","year":"2014","journal-title":"Micron"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Arango Duque, G., and Descoteaux, A. (2014). Macrophage cytokines: Involvement in immunity and infectious diseases. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00491"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/ptr.7407","article-title":"Berberine as a natural modulator of inflammatory signaling pathways in the immune system: Focus on NF-\u03baB, JAK\/STAT, and MAPK signaling pathways","volume":"36","author":"Haftcheshmeh","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a keystone cytokine in health and disease","volume":"1","author":"Hunter","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Scheller, J., Chalaris, A., Schmidt-Arras, D., and Rose-John, S. (2011). The pro-and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta (BBA) Mol. Cell Res., 1813.","DOI":"10.1016\/j.bbamcr.2011.01.034"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Merecz-Sadowska, A., Sitarek, P., \u015aliwi\u0144ski, T., and Zajdel, R. (2020). Anti-inflammatory activity of extracts and pure compounds derived from plants via modulation of signaling pathways, especially PI3K\/AKT in macrophages. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249605"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"153472","DOI":"10.1016\/j.phymed.2021.153472","article-title":"Shizukaol A exerts anti-inflammatory effect by regulating HMGB1\/Nrf2\/HO-1 pathway","volume":"82","author":"Tang","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.coph.2009.04.008","article-title":"Anti-inflammatory and pro-inflammatory roles of TGF-\u03b2, IL-10, and IL-22 in immunity and autoimmunity","volume":"9","author":"Sanjabi","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1177\/0022034510378683","article-title":"Epigenetic mechanisms in inflammation","volume":"90","author":"Bayarsaihan","year":"2011","journal-title":"J. Dent. Res."},{"key":"ref_39","unstructured":"Zhang, R., Li, J., Zhang, T., Niu, J., and Li, X. (2020). Dihydroquercetin inhibits LPS-induced inflammation by activating AMPK\/Nrf2\/HO-1 pathway in RAW264.7 macrophages. Front. Pharmacol., 11."},{"key":"ref_40","unstructured":"Tang, Y., Zhang, J., Dai, Y., and Xiong, H. (2018). Nardochinoid C inhibits inflammation via activating Nrf2\/HO-1 signaling pathway. Front. Pharmacol., 9."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev-immunol-051116-052424","article-title":"Mucosal ecological network of epithelium and immune cells for gut homeostasis and tissue healing","volume":"35","author":"Kurashima","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lacina, L., Kol\u00e1\u0159, M., Pfeiferov\u00e1, L., G\u00e1l, P., and Smetana, K. (2024). Wound healing: Insights into autoimmunity, ageing, and cancer ecosystems through inflammation and IL-6 modulation. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1403570"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"594","DOI":"10.31254\/jsir.2014.3609","article-title":"RP-HPLC method development and validation of Quercetin isolated from the plant Tridax procumbens L.","volume":"3","author":"Sanghavi","year":"2014","journal-title":"J. Sci. Innov. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"130","DOI":"10.2144\/97221bi01","article-title":"Continuous fluorescence monitoring of rapid cycle DNA amplification","volume":"22","author":"Wittwer","year":"1997","journal-title":"BioTechniques"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/15\/2346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:18:29Z","timestamp":1760033909000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/15\/2346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":46,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["plants14152346"],"URL":"https:\/\/doi.org\/10.3390\/plants14152346","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]}}}