Abstract

BackgroundViola yedoensis (VY, Violaceae) is a popular medicinal herb used in traditional eastern medicine for treating lots of diseases, including inflammation and its related symptoms. However, the anti-inflammatory properties of VY have not been demonstrated. In the present study, we investigated the anti-inflammatory effects of VY ethanol extract (VYE) on macrophages and attempted to identify the bioactive components of VYE.MethodsWe assessed the effects of VYE on secretion of nitric oxide (NO) and inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. In addition, we explored the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and changes in heme oxygenase (HO)-1, nuclear factor (NF)-kB, and mitogen-activated protein kinase (MAPK) signaling pathways in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In addition, a rapid and useful approach to identify potential bioactive components in VYE with anti-inflammatory effects was developed using murine macrophage cell extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS).ResultsWe found that VYE exerted anti-inflammatory activity by inhibiting the production of key inflammation mediators and related products, as well as suppression of HO-1, NF-kB, and MAPK signaling pathway activation in RAW 264.7 cells. In addition, we identified two compounds in VYE via the cell extraction method.ConclusionsOur results revealed that VYE exerts anti-inflammatory activities and its detailed inhibitory mechanism in macrophages. Furthermore, we identified bioactive components of VYE.

Highlights

  • Viola yedoensis (VY, Violaceae) is a popular medicinal herb used in traditional eastern medicine for treating lots of diseases, including inflammation and its related symptoms

  • VY ethanol extract (VYE) strongly represses inducible nitric oxide synthase (iNOS) but not COX-2 upon LPS stimulation and induces heme oxygenase (HO)-1 in RAW 264.7 macrophages To examine the mechanism by which VYE reduces nitric oxide (NO) and cytokine production by LPS stimulation, we evaluated the effect of VYE on iNOS, COX-2, and HO1 expression in RAW 264.7 macrophages

  • The expression of NO and iNOS was due to a direct influence on the induction of HO-1 [31], we further investigated the effect of VYE treatment on HO-1 expression

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Summary

Introduction

Viola yedoensis (VY, Violaceae) is a popular medicinal herb used in traditional eastern medicine for treating lots of diseases, including inflammation and its related symptoms. VY is a well-known herb in traditional oriental medicine used for the treatment of inflammation-related diseases including swelling, sores, boils, furuncles, Inflammation is a first host immune response to protect the body from injury or infection. Inflammatory cytokine production and release in response to LPS is mediated by the activation of NF-kB and MAPK in macrophages [11, 12]. NF-kB and MAPKs are typical inflammatory signaling pathways in macrophages. These two pathways induce pro-inflammatory cytokines and release a wide range of inflammatory mediators. The majority of targets for the development of therapeutic approaches to treat various inflammatory diseases are associated with inhibition of these pathways

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