IKK β -Targeted Anti-Inflammatory Activities of a Butanol Fraction of Artificially Cultivated Cordyceps pruinosa Fruit Bodies.

Han Gyung Kim,Tae Woong Kim,Ji Hye Kim,Jae Mo Sung,Jong-Hoon Kim,Sungjae Yang,Yung Chul Park,Sungyoul Hong,Woo Seok Yang,Eunji Kim,Deok Hyo Yoon,Jae Youl Cho,Gi-Ho Sung,Gwang-Soo Baek

doi:10.1155/2014/562467

Abstract

The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were investigated by determining inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp-BF were investigated by identifying target enzymes using biochemical and molecular biological approaches. Cp-BF strongly inhibited the production of NO and TNF-α, release of reactive oxygen species (ROS), phagocytic uptake of FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO synthase (iNOS), and tumour necrosis factor-alpha (TNF)-α in activated RAW264.7 cells. Cp-BF also strongly downregulated the NF-κB pathway by suppressing IKKβ according to luciferase reporter assays and immunoblot analysis. Furthermore, Cp-BF blocked both increased levels of NF-κB-mediated luciferase activities and phosphorylation of p65/p50 observed by IKKβ overexpression. Finally, orally administered Cp-BF was found to attenuate gastric ulcer and block the phosphorylation of IκBα induced by HCl/EtOH. Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may be mediated by suppression of IKKα and its downstream NF-κB activation. Since our group has established the mass cultivation conditions by developing culture conditions for Cordyceps pruinosa, the information presented in this study may be useful for developing new anti-inflammatory agents.

Highlights

Inflammation is a complicated defensive response against various infecting pathogens and toxins and serves as one of the body’s innate immunity barriers
In the present study, we evaluated the anti-inflammatory mechanism of a butanol extract (Cp-BF) of the Cordyceps pruinosa fruit body
Similar to a previous study of a methanol extract of the Cordyceps pruinosa fruit body, we found that Cordyceps pruinosa butanol fraction (Cp-BF) could suppress the functional activation of macrophages in inflammatory responses

Summary

Introduction

Inflammation is a complicated defensive response against various infecting pathogens and toxins and serves as one of the body’s innate immunity barriers. Evidence-Based Complementary and Alternative Medicine will generate intracellular signalling events through nonreceptor type protein tyrosine kinases, including Syk, Src, phosphoinositide-3-kinase (PI3K), and mitogen activated protein kinase (MAPK), upstream of extracellular signalrelated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). All of these intracellular responses reach activation of transcription factors including CREB, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) [1, 2]. Development of stronger and safer anti-inflammatory remedies may contribute to more promising strategies to effectively treat inflammation-derived diseases

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