PMID- 30233137 OWN - NLM STAT- MEDLINE DCOM- 20190212 LR - 20220321 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 12 DP - 2018 TI - Dingchuan tang essential oil inhibits the production of inflammatory mediators via suppressing the IRAK/NF-kappaB, IRAK/AP-1, and TBK1/IRF3 pathways in lipopolysaccharide-stimulated RAW264.7 cells. PG - 2731-2748 LID - 10.2147/DDDT.S160645 [doi] AB - BACKGROUND: Dingchuan tang (asthma-relieving decoction), a formula of nine herbs, has been used for treating respiratory inflammatory diseases for >400 years in the People's Republic of China. However, the mechanisms underlying the anti-inflammatory action of dingchuan tang is not fully understood. This study aims to investigate the effects of Dingchuan tang essential oil (DCEO) on inflammatory mediators and the underlying mechanism of action. MATERIALS AND METHODS: DCEO was extracted by steam distillation. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were used as the cell model. Production of nitric oxide (NO) was determined by the Griess test. Protein secretion and mRNA levels of inflammatory mediators were measured by the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Protein levels were examined by Western blot. Nuclear localization of nuclear factor-kappa B (NF-kappaB) was detected using immunofluorescence analyses. RESULTS: DCEO significantly reduced LPS-triggered production of NO and prostaglandin E2 (PGE2) and decreased protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). LPS induced upregulation of protein and mRNA levels of cytokines (interleukin-1beta [IL-1beta], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-alpha]), and chemokines (monocyte chemoattractant protein-1 [MCP-1], chemokine [C-C motif] ligand 5 [CCL-5], and macrophage inflammatory protein [MIP]-1alpha) were suppressed by DCEO treatment. Phosphorylation and nuclear protein levels of transcription factors (activator protein-1 [AP-1], NF-kappaB, interferon regulatory factor 3 [IRF3]) were decreased by DCEO. Protein levels of phosphorylated IkappaB-alpha, IkappaB kinase alpha/beta (IKKalpha/beta), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), TGF beta-activated kinase 1 (TAK1), TANK-binding kinase 1 (TBK1), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) were lowered by DCEO. Moreover, degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 induced by LPS was inhibited by DCEO treatment. CONCLUSION: Suppression of the interleukin-1 receptor-associated kinase (IRAK)/NF-kappaB, IRAK/AP-1 and TBK1/IRF3 pathways was associated with the inhibitory effects of DCEO on inflammatory mediators in LPS-stimulated RAW264.7 macrophages. This study provides a pharmacological justification for the use of dingchuan tang in managing inflammatory disorders. FAU - Zhang, Yi AU - Zhang Y AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. AD - Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, People's Republic of China. FAU - Guo, Hui AU - Guo H AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. FAU - Cheng, Brian Chi-Yan AU - Cheng BC AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. FAU - Su, Tao AU - Su T AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. FAU - Fu, Xiu-Qiong AU - Fu XQ AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. FAU - Li, Ting AU - Li T AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. FAU - Zhu, Pei-Li AU - Zhu PL AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. FAU - Tse, Kai-Wing AU - Tse KW AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. FAU - Pan, Si-Yuan AU - Pan SY AD - Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, People's Republic of China, zlyu@hkbu.edu.hk. FAU - Yu, Zhi-Ling AU - Yu ZL AD - Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, zlyu@hkbu.edu.hk. AD - Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, People's Republic of China, zlyu@hkbu.edu.hk. AD - Consun Chinese Medicines Research Centre for Renal Diseases, Hong Kong Baptist University, Hong Kong, People's Republic of China, zlyu@hkbu.edu.hk. LA - eng PT - Journal Article DEP - 20180904 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Inflammation Mediators) RN - 0 (Interferon Regulatory Factor-3) RN - 0 (Irf3 protein, mouse) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Oils, Volatile) RN - 0 (Plant Extracts) RN - 0 (Transcription Factor AP-1) RN - 0 (dingchuan tang) RN - EC 2.7.1.- (Tbk1 protein, mouse) RN - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases) RN - EC 2.7.11.1 (Irak1 protein, mouse) RN - EC 2.7.11.1 (Irak4 protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Animals MH - Cell Survival/drug effects MH - Enzyme-Linked Immunosorbent Assay MH - Inflammation Mediators/antagonists & inhibitors/metabolism MH - Interferon Regulatory Factor-3/antagonists & inhibitors/metabolism MH - Interleukin-1 Receptor-Associated Kinases/antagonists & inhibitors/metabolism MH - Lipopolysaccharides/*pharmacology MH - Macrophages/drug effects/metabolism MH - Mice MH - NF-kappa B/antagonists & inhibitors/metabolism MH - Oils, Volatile/*pharmacology MH - Plant Extracts/*chemistry MH - Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism MH - RAW 264.7 Cells MH - Real-Time Polymerase Chain Reaction MH - Transcription Factor AP-1/antagonists & inhibitors/metabolism PMC - PMC6129014 OTO - NOTNLM OT - anti-inflammation OT - molecular pathways OT - respiratory diseases OT - traditional Chinese medicine COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/09/21 06:00 MHDA- 2019/02/13 06:00 PMCR- 2018/09/04 CRDT- 2018/09/21 06:00 PHST- 2018/09/21 06:00 [entrez] PHST- 2018/09/21 06:00 [pubmed] PHST- 2019/02/13 06:00 [medline] PHST- 2018/09/04 00:00 [pmc-release] AID - dddt-12-2731 [pii] AID - 10.2147/DDDT.S160645 [doi] PST - epublish SO - Drug Des Devel Ther. 2018 Sep 4;12:2731-2748. doi: 10.2147/DDDT.S160645. eCollection 2018.