Anti-inflammatory activity of the extracts from Rodgersia podophylla leaves through activation of Nrf2/HO-1 pathway, and inhibition of NF-κB and MAPKs pathway in mouse macrophage cells

Inflamm Res. 2020 Feb;69(2):233-244. doi: 10.1007/s00011-019-01311-2. Epub 2020 Jan 6.

Abstract

Objective: Recently, Rodgersia podophylla has been reported to exhibit anti-inflammatory activity. However, little is known about the potential mechanisms about its anti-inflammatory activity. We elucidated the anti-inflammatory mechanisms of leaves extracts from Rodgersia podophylla (RP-L) in RAW264.7 cells.

Materials and methods: LPS-induced NO was measured by Griess and mRNA of pro-inflammatory mediators was analyzed by RT-PCR. Cell viability was measured using MTT assay. The protein level was analyzed by Western blot.

Results: RP-L significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, IL-1β and IL-6 in LPS-stimulated RAW264.7 cells. RP-L increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of RP-L against LPS-induced NO production in RAW264.7 cells. Inhibition of p38, ROS and GSK3β attenuated RP-L-mediated HO-1 expression. Inhibition of ROS inhibited p38 phosphorylation and GSK3β expression induced by RP-L. In addition, inhibition of GSK3β blocked RP-L-mediated p38 phosphorylation. RP-L induced nuclear accumulation of Nrf2, and inhibition of p38, ROS and GSK3β abolished RP-L-mediated nuclear accumulation of Nrf2. Furthermore, RP-L blocked LPS-induced degradation of IκB-α and nuclear accumulation of p65. RP-L also attenuated LPS-induced phosphorylation of ERK1/2 and p38. In GC/MS analysis of RP-L, pyrogallol was detected as bioactive compound for anti-inflammatory activity of RP-L. Pyrogallol was observed to activate HO-1 expression through ROS/GSK3β/p38/Nrf2/HO-1 signaling.

Conclusions: Our results suggest that RP-L exerts potential anti-inflammatory activity by activating ROS/GSK3β/p38/Nrf2/HO-1 signaling and inhibiting NF-κB and MAPK signaling in RAW264.7 cells. These findings suggest that RP-L may have great potential for the development of anti-inflammatory drug.

Keywords: Anti-inflammation; HO-1; MAPKs; Nf-κb; Rodgersia podophylla.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Heme Oxygenase-1 / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects*
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / drug effects*
  • Nitric Oxide / biosynthesis
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • RAW 264.7 Cells
  • Saxifragaceae / chemistry*
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Plant Extracts
  • Nitric Oxide
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Mitogen-Activated Protein Kinases