Anti-inflammatory effect of Cortex Eucommiae via modulation of the toll-like receptor 4 pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages. (14th September 2017)

• Record Type: Journal Article
• Authors: Koh, Wonil; Shin, Joon-Shik; Lee, Jinho; Lee, In-Hee; Lee, Sang Kook; Ha, In-Hyuk; Chung, Hwa-Jin
• Is Part Of: Journal of ethnopharmacology. Volume 209(2017)
• Page Start: 255
• Page End: 263
• Publication Date: 2017-09-14
• Subjects: CE Cortex Eucommiae -- LPS lipopolysaccharide -- HPLC high-performance liquid chromatography -- RT-PCR reverse transcriptase-polymerase chain reaction -- IC50 inhibitory concentration of 50% -- TLR-4 toll-like receptor 4 -- Myd88 myeloid differentiation primary response gene 88 -- TRIF toll-interleukin receptor domain-containing-adapter-inducing interferon-β -- iNOS inducible nitric oxide synthase -- NO nitric oxide -- COX-2 cyclooxygenase-2 -- TNF-α tumor necrosis factor-α -- IL-1β interleukin-1β -- NF-κB nuclear factor-κB -- IκB inhibitor of NF-κB -- IKK IκB kinase complex -- MAPKs mitogen-activated protein kinases -- PI3K phosphoinositide 3-kinase -- mTOR mammalian target of rapamycin -- IFN-β interferon-β -- IRF interferon regulatory factor -- STATs signal transducers and activators of transcription; Cortex Eucommiae -- Anti-inflammatory -- RAW 264.7 cells -- TLR-4 -- Myd88; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2017.08.001
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmocological relevance: Cortex Eucommiae (CE), the bark of Eucommia ulmoides Oliv., has been traditionally used for its kidney-tonifying and bone- and tendon-enhancing properties in Korea, China, and Japan. CE has been historically prescribed for inflammatory conditions such as arthritis of the knee and ankle. Aim of the study: Although CE has recently been shown to suppress inflammation in scientific studies, whether this effect involves modulation of the toll-like receptor 4 (TLR-4) pathway is currently unknown. Materials and methods: The modulatory effect of CE on the TLR-4 pathway, both myeloid differentiation primary response gene 88 (Myd88)-dependent and independent, was investigated through real-time reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, and a reporter gene assay in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Results: CE dose-dependently inhibited nitric oxide production without significant cytotoxicity with an IC50 of 356.23 μg/mL. In addition, CE down-regulated both LPS-induced mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in a dose-dependent manner. CE suppressed LPS-induced activation of nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathways, which together comprise the Myd88-dependent TLR-4 pathway. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was also down-regulated by CE in a dose-dependent manner. CE additionally suppressed LPS-induced activation of interferon-β (IFN-β) and signal transducer and activator of transcription (STAT) pathway, which is associated with the Myd88-independent TLR-4 pathway. Conclusions: CE down-regulated both Myd88-dependent and independent TLR-4 pathways, thus exerting anti-inflammatory effects. These results suggest that CE may be used as a potential therapeutic agent against chronic inflammatory diseases. Graphical abstract: