Inhibitory Effects of Aucklandia lappa Decne. Extract on Inflammatory and Oxidative Responses in LPS-Treated Macrophages

Molecules. 2020 Mar 15;25(6):1336. doi: 10.3390/molecules25061336.

Abstract

Aucklandia lappa Decne., known as "Mok-hyang" in Korea, has been used for the alleviation of abdominal pain, vomiting, diarrhea, and stress gastric ulcers in traditional oriental medicine. We investigated the anti-inflammatory and antioxidative effects of the ethanol extract of Aucklandia lappa Decne. (ALDE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. ALDE significantly inhibited the LPS-induced nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. The production of other proinflammatory mediators, including COX-2, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, was reduced by ALDE in LPS-stimulated RAW 264.7 cells. The mechanism underlying the anti-inflammatory effects of ALDE was elucidated to be the suppression of LPS-induced nuclear translocation of p65, followed by the degradation of IκB and the inhibition of the phosphorylation of mitogen-activated protein kinases (MAPK). In addition, ALDE showed enhanced radical scavenging activity. The antioxidant effect of ALDE was caused by the enhanced expression of heme oxygenase (HO-1) via stabilization of the expression of the nuclear transcription factor E2-related factor 2 (Nrf2) pathway. Collectively, these results indicated that ALDE not only exerts anti-inflammatory effects via the suppression of the NF-κB and MAPK pathways but also has an antioxidative effect through the activation of the Nrf2/HO-1 pathway.

Keywords: Aucklandia lappa Decne. extract; cyclooxygenase-2; heme oxygenase-1; inducible nitric oxide; lipopolysaccharide; macrophage; mitogen-activated protein kinase; nitric oxide; nuclear factor-κB.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / metabolism
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Heme Oxygenase-1 / metabolism
  • I-kappa B Proteins / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells
  • Saussurea / chemistry*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • I-kappa B Proteins
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Plant Extracts
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases