title: A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos inhibits the production of inflammatory mediators and the IRAK-1/TAK1 and TBK1/IRF3 pathways in RAW 264.7 and THP-1 cells.
abstract: BACKGROUND
  As documented in the Chinese Materia Medica Grand Dictionary (), a herbal formula (RL) consisting of Rosae Multiflorae Fructus (multiflora rose hips) and Lonicerae Japonicae Flos (Japanese honeysuckle flowers) has traditionally been used in treating inflammatory disorders. RL was previously reported to inhibit the expression of various inflammatory mediators regulated by NF-κB and MAPKs that are components of the TLR4 signalling pathways.
  
  
  OBJECTIVE
  This study aims to provide further justification for clinical application of RL in treating inflammatory disorders by further delineating the involvement of the TLR4 signalling cascades in the effects of RL on inflammatory mediators.
  
  
  METHODS
  RL consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos (in 5:3 ratio) was extracted using absolute ethanol. We investigated the effect of RL on the production of cytokines and chemokines that are regulated by three key transcription factors of the TLR4 signalling pathways AP-1, NF-κB and IRF3 in LPS-stimulated RAW264.7 cells using the multiplex biometric immunoassay. Phosphorylation of AP-1, NF-κB, IRF3, IκB-α, IKKα/β, Akt, TAK1, TBK1, IRAK-1 and IRAK-4 were examined in LPS-stimulated RAW264.7 cells and THP-1 cells using Western blotting. Nuclear localizations of AP-1, NF-κB and IRF3 were also examined using Western blotting.
  
  
  RESULTS
  RL reduced the secretion of various pro-inflammatory cytokines and chemokines regulated by transcription factors AP-1, NF-κB and IRF3. Phosphorylation and nuclear protein levels of these transcription factors were decreased by RL treatment. Moreover, RL inhibited the activation/phosphorylation of IκB-α, IKKα/β, TAK1, TBK1 and IRAK-1.
  
  
  CONCLUSIONS
  Suppression of the IRAK-1/TAK1 and TBK1/IRF3 signalling pathways was associated with the effect of RL on inflammatory mediators in LPS-stimulated RAW264.7 and THP-1 cells. This provides further pharmacological basis for the clinical application of RL in the treatment of inflammatory disorders.
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Brian Chi Yan
authors: BC
authors: Cheng
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Hua
authors: H
authors: Yu
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Tao
authors: T
authors: Su
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Xiu-Qiong
authors: XQ
authors: Fu
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Hui
authors: H
authors: Guo
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Ting
authors: T
authors: Li
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Hui-Hui
authors: HH
authors: Cao
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Anfernee Kai-Wing
authors: AK
authors: Tse
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Hiu-Yee
authors: HY
authors: Kwan
authors: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong. Electronic address: zlyu@hkbu.edu.hk.
authors: Zhi-Ling
authors: ZL
authors: Yu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D031239:Lonicera; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D028321:Plant Preparations / Q000302:isolation & purification / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D027826:Rosa; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D050838:Interferon Regulatory Factor-3; D053592:Interleukin-1 Receptor-Associated Kinases; D020930:MAP Kinase Kinase Kinases; D010936:Plant Extracts; D028321:Plant Preparations; D017346:Protein Serine-Threonine Kinases; D000099151:MAP Kinase Kinase Kinase 7; C494233:Irf3 protein, mouse; C498588:Tbk1 protein, mouse
keywords: Anti-inflammation; Chlorogenic acid (PubChem CID: 1794427); Gallic acid (PubChem CID: 370); IRAK-1; Lipopolysaccharide (PubChem CID: 11970143); Lonicera japonica; Rosa multiflora; TBK1; TLR4