Abstract

BackgroundSC-E1 is a novel herbal formula consisting of five oriental medicinal herbs used frequently in traditional herbal medicine for the treatment of inflammatory diseases in Korea. This study examined the effects of SC-E1 on lipopolysaccharide (LPS)-stimulated macrophages and the molecular mechanism involved.MethodsThe cytotoxic effect of the SC-E1 extract was evaluated in RAW 264.7 cells by MTT assay. The effects of SC-E1 on the free radical scavenging and generation of intracellular reactive oxygen species were measured using DPPH and DCFH-DA, respectively. The effects of SC-E1 on the production of pro-inflammatory cytokines, inflammatory mediators, and related products were determined by ELISA and western blotting. The molecular mechanism and the nuclear translocation of nuclear factor-kappa B (NF-κB) and NF-E2-related factor 2 (Nrf2) were examined by western blot analysis and immunocytochemistry.ResultsSC-E1 exhibited strong anti-oxidant activity and inhibited LPS-induced NO secretion as well as iNOS expression and the production of pro-inflammatory cytokines, without affecting the cell viability. SC-E1 also suppressed the LPS-induced NF-κB activation and the mitogen-activated protein kinase (MAPK) pathway. Moreover, SC-E1 induced heme oxygenase-1 (HO-1) expression via the nuclear translocation of Nrf2. The inhibitory effects of SC-E1 on the production of pro-inflammatory cytokines were abrogated by treatment with SnPP, an HO-1 inhibitor.ConclusionThese results suggest that SC-E1 exerts its anti-oxidant and anti-inflammatory effects through the inhibition of NF-κB and MAPK as well as Nrf2-mediated HO-1 induction in macrophages. These findings provide evidences for SC-E1 to be considered as a new prescription for treating inflammatory diseases.

Highlights

  • SC-E1 is a novel herbal formula consisting of five oriental medicinal herbs used frequently in traditional herbal medicine for the treatment of inflammatory diseases in Korea

  • High-performance liquid chromatography (HPLC) analysis of SC-E1 To conduct a quantitative HPLC analysis of SC-E1, the two compounds, geniposide from Gardenia jasminoides and puerarin from Pueraria lobata, were selected as the marker compounds for quality control

  • Effect of SC-E1 on Nuclear factor-kappa B (NF-κB) activation in LPS-stimulated RAW 264.7 macrophages To further determine the mechanism underlying the anti-inflammatory effects of SC-E1, this study examined whether SC-E1 controls the activation of NF-κB signaling, relating to regulation of the expression of inflammatory mediators and cytokines [30]

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Summary

Introduction

SC-E1 is a novel herbal formula consisting of five oriental medicinal herbs used frequently in traditional herbal medicine for the treatment of inflammatory diseases in Korea. Inflammation is a complex immune response that protects the body from infections or tissue injury and involves the activation of various immune cells, such as macrophages, neutrophils, and lymphocytes [1]. NO and PGE2 are synthesized by inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively [6, 7]. These inflammatory mediators and cytokines are essential for host survival after an infection as well as for the repair of tissue damage, their excessive production is associated with a range of inflammatory disorders [5, 8]

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