Wen-Pi-Tang-Hab-Wu-Ling-San extract inhibits the release of inflammatory mediators from LPS-stimulated mouse macrophages

Aim of the study: Wen-Pi-Tang is a traditional herbal prescription that has been used traditionally for the treatment of various inflammatory diseases, including chronic renal failure, renal injury, renal tubular cell damage and diabetic nephropathy. In this study, we investigated the pharmacological activity of modified Wen-Pi-Tang, Wen-Pi-Tang-Hab-Wu-Ling-San (WHW) extract. Materials and methods: Production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), IL-6 and NO in supernatant, mRNA expression of TNF-alpha, IL-1 beta, IL-6 and iNOS, protein expression of iNOS, phosphorylation of mitogen-activated protein kinases (MAPKs) and activation of nuclear factor-kappa B in the extract were assayed. Results: We found that WHW extract had potent anti-inflammatory effects in LPS-stimulated RAW264.7 cells and primary peritoneal macrophages. WHW extract strongly inhibited the excessive production of inflammatory mediators, nitric oxide (NO), TNF-alpha (TNF-alpha), interleukin 1-beta (IL-1 beta) and IL-6 in LPS-stimulated macrophages. The inhibition of inducible nitric oxide synthase (iNOS) and these cytokines resulted from the reduced expressions of mRNAs of iNOS and these cytokines, respectively. WHW extract attenuated the phosphorylation of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases I and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK), as well as the activation of nuclear factor-kappa B (NF-kappa B) in LPS-stimulated RAW264.7 cells. Conclusions: These data suggest that WHW extract may exhibit anti-inflammatory effects through the modulation of MAPK and the NF-kappa B-dependent pathway involved in inflammation. (c) 2007 Elsevier Ireland Ltd. All rights reserved.