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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

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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.

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Abbreviations

CO:

Carbon monoxide

COX-2:

Cyclooxygenase-2

DMSO:

Dimethyl sulfoxide

ERK1/2:

Extracellular signal-regulated kinases 1/2

GSK3β:

Glycogen synthase kinase 3 beta

HO-1:

Heme oxygenase-1

IKK:

IκB kinase

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

iNOS:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharide

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

JNK:

C-Jun N-terminal kinases

MAPKs:

Mitogen-activated protein kinases

NAC:

N-Acetyl-l-cysteine

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

Nrf2:

NF-E2-related factor 2

NSAIDs:

Nonsteroidal anti-inflammatory drugs

PI3K:

Phosphoinositide 3-kinase

ROS:

Reactive oxygen species

RP-L:

Leave extracts from Rodgersia podophylla

RT-PCR:

Reverse transcriptase-polymerase chain reaction

ZnPP:

Zinc protoporphyrin IX

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Acknowledgements

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713 and NRF-2018R1A6A1A03024862).

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Author notes

  1. Ha Na Kim and Jeong Dong Kim equally contributed to this work

Authors and Affiliations

  1. Department of Medicinal Plant Resources, Andong National University, Andong, 36729, Republic of Korea

    Ha Na Kim, Jeong Dong Kim, Su Bin Park & Jin Boo Jeong

  2. Forest Medicinal Resources Research Center, National Institute of Forest Science, Yongju, 36040, Republic of Korea

    Ho-Jun Son, Gwang Hun Park & Hyun Ji Eo

  3. Department of Food Science and Biotechnology, Kyonggi University, Suwon, 16227, Republic of Korea

    Hyun-Seok Kim

  4. Agricultural Science and Technology Research Institute, Andong National University, Andong, 36729, Republic of Korea

    Jin Boo Jeong

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  1. Ha Na Kim
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Kim, H.N., Kim, J.D., Park, S.B. et al. 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. 69, 233–244 (2020). https://doi.org/10.1007/s00011-019-01311-2

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