Abstract

BackgroundOryeongsan (OR) is an herbal medication used in east-Asian traditional medicine to treat dysuresia, such as urinary frequency, hematuria, and dysuria due to renal disease and chronic nephritis. Recent studies showed that protective effect against acute gastric mucosal injury and an inhibitory effect on the renin-angiotensin-aldosterone pathway of OR. However, its effect on inflammation still remains unknown. In this study, to provide insight into the biological effects of OR, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in the RAW 264.7 macrophage cells.MethodsWe investigated the pharmacological and biological effects of OR on the production of pro-inflammatory cytokines, inflammatory mediators, and related products through Enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Also, we examined the activation and suppression of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) pathways in LPS-stimulated macrophages via Western blot analysis in order to explore inhibitory mechanism of OR.ResultsOR had anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta. In addition, it strongly suppressed cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), NO synthesizing enzymes. It also induced heme oxygenase (HO)-1 expression and inhibited NF-kappaB signaling pathway activation and phosphorylation of MAPKs.ConclusionsWe further demonstrate the anti-inflammatory effects and inhibitory mechanism of OR in LPS-stimulated macrophages for the first time. OR contains strong anti-inflammatory activity and affects various mechanism pathways including NF-kappaB, MAPKs and HO-1. Our results suggest that OR has potential value to be developed as an inflammatory therapeutic agent from a natural substance.

Highlights

  • Oryeongsan (OR) is an herbal medication used in east-Asian traditional medicine to treat dysuresia, such as urinary frequency, hematuria, and dysuria due to renal disease and chronic nephritis

  • We investigated whether OR-induced modulation of nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) signaling pathways and their influence on heme oxygenase (HO)-1 induction were responsible for the anti-inflammatory effects of OR

  • Because MAPKs activated by LPS are related to inducible nitric oxide synthase (iNOS) expression in macrophages [46], we examined the inhibitory effect of OR on the phosphorylation of MAPKs

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Summary

Introduction

Oryeongsan (OR) is an herbal medication used in east-Asian traditional medicine to treat dysuresia, such as urinary frequency, hematuria, and dysuria due to renal disease and chronic nephritis. Recent studies showed that protective effect against acute gastric mucosal injury and an inhibitory effect on the renin-angiotensinaldosterone pathway of OR. OR is a traditional ancient herbal medication in East Asia. It is a prescription described in the Sanghanron, an ancient Chinese medical book. A previous study demonstrated that OR protects against ethanol-induced acute gastric mucosal injury [1]. Another study revealed that OR has an inhibitory effect on the renin-angiotensin-aldosterone system in rats [2]. It has been reported that OR exert protective effect on adriamycin-induced nephrotic syndrome in rats [4].

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