Chamaecyparis obtusa (Siebold & Zucc.) Endl. leaf extracts prevent inflammatory responses via inhibition of the JAK/STAT axis in RAW264.7 cells. (10th January 2022)

• Record Type: Journal Article
• Authors: Kwon, Yong-Jin; Seo, Eun-Bi; Kim, Seul-Ki; Noh, Kum Hee; Lee, Haeri; Joung, Yeo-Won; Shin, Hyun Mu; Jang, Young-Ah; Kim, Yu Mi; Lee, Jin-Tae; Ye, Sang-Kyu
• Is Part Of: Journal of ethnopharmacology. Volume 282(2021)
• Publication Date: 2022-01-10
• Subjects: Chamaecyparis obtusa (Siebold & zucc.) endl. (C. obtusa) -- Macrophage -- Inflammatory response -- Janus kinase (JAK) -- Signaling transducer and activator of transcription (STAT) -- Pro-inflammatory mediators; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.114493
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Chamaecyparis obtusa (Siebold & Zucc.) Endl. ( C. obtusa ) has been used as folk medicine in East Asia and has been reported to alleviate inflammatory diseases. However, the detailed mechanisms for the anti-inflammatory effects of C. obtusa remain unclear. Aim of the study: Although the anti-inflammatory mechanisms of natural products have been studied for decades, it is still important to identify the potential anti-inflammatory effects of natural sources. In this study, we investigated the anti-inflammatory effects and underlying mechanism of C. obtusa leaf extracts. Material &methods: The cell viability was determined by MTT and crystal violet staining. NO production in the supernatant was measured using Griess reagent. The cell lysates were analyzed by immunoblotting and RT-qPCR. Secreted cytokines were analyzed using ELISA kit and cytokine array kit. mRNA expression from the GSE9632 database set. Z-scores were calculated for each gene and visualized by heat map. Results: Among the extracts of C. obtusa obtained with different extraction methods, the 99% ethanol leaf extract (CO99EL) strongly inhibited lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and Janus kinase/signaling transducer and activator of transcription (JAK/STAT) phosphorylation in RAW264.7 cells. In addition, CO99EL strongly inhibited LPS-induced interleukin (IL)-1β, IL-6, IL-27, and C-C motif chemokine ligand (CCL)-1 production and directly inhibited LPS-induced JAK/STAT phosphorylation in RAW264.7 cells. Conclusions: These findings demonstrate that CO99EL significantly prevents LPS-induced macrophage activation by inhibiting the JAK/STAT axis. Therefore, we suggest the use of C. obtusa extracts as therapeutic approach for inflammatory diseases. Graphical abstract: Image 1 Highlights: The cytotoxicity of the leaf extracts was lower and the yields were higher than for the other C. obtusa extracts. CO99EL had remarkably potent anti-inflammatory effects among the C. obtusa leaf extracts in RAW264.7 cells. CO99EL inhibited LPS-induced JAK/STAT by inhibiting pro-inflammatory secreted molecules in RAW264.7 cells. CO99EL directly inhibited JAK/STAT activation in RAW264.7 cells.