Anti-inflammatory effect of Cortex Eucommiae via modulation of the toll-like receptor 4 pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages.

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 356.23μg/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.

journal_name

J Ethnopharmacol

authors

Koh W,Shin JS,Lee J,Lee IH,Lee SK,Ha IH,Chung HJ

doi

10.1016/j.jep.2017.08.001

subject

Has Abstract

pub_date

2017-09-14 00:00:00

pages

255-263

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(17)31106-6

journal_volume

209

pub_type

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