Abstract

BackgroundPoria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Although several studies have demonstrated the anti-inflammatory activity of this fungus, its underlying mechanisms have not yet been clearly defined.MethodsIn the present study, we have demonstrated the anti-inflammatory effects of ethanol extract of P. cocos (EEPC) in lipopolysaccaride (LPS)-stimulated RAW 264.7 macrophages. As inflammatory parameters, the productions of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were evaluated. We also examined the EEPC’s effect on the nuclear factor-kappaB (NF-κB) signaling pathway.ResultsOur results indicated that EEPC exhibits a potent inhibitory effect on NO production and inhibits PGE2 release in LPS-induced macrophages without affecting cell viability. EEPC also significantly attenuated LPS-induced secretion of inflammatory cytokines IL-1β and TNF-α. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1β, and TNF-α was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits, which correlated with EEPC’s inhibitory effects on inhibitor kappaB (IκB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-κB, as well as the nuclear translocation of the NF-κB p65, which correlated with EEPC’s inhibitory effects on inhibitor kappaB (IκB) degradation.ConclusionsTaken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.

Highlights

  • Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials

  • nitric oxide synthase (NOS) are comprised of three members, including endothelial NOS, neuronal NOS, and inducible NOS, which makes nitric oxide (NO) from L-arginine, and COX exists as two isozymes, COX-1 and COX-2, converting arachidonic acid into prostaglandins (PGs)

  • As a part of our on-going screening program to evaluate the anti-inflammatory potentials of medicinal mushrooms, we investigated the anti-inflammatory properties of an ethanol extract of P. cocos (EEPC) and the responsible underlying molecular mechanisms involved in an LPS-stimulated RAW 264.7 murine macrophage model

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Summary

Introduction

Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Key pro-inflammatory stimuli including bacterial lipopolysaccharide (LPS), mitogens, and cytokines modulate their effects by inducing the activation of nuclear factor-kappaB (NF-κB), which regulates the expression of many genes involved in immune and inflammatory responses [9,10]. For this reason, inhibition of proinflammatory mediators and cytokines by these NF-κB response genes has been proposed to be a good approach for the treatment of various inflammatory diseases [11,12]

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