Inflammation

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Nardosinone-Type Sesquiterpenes from the Hexane Fraction of Nardostachys jatamansi Attenuate NF-κB and MAPK Signaling Pathways in Lipopolysaccharide-Stimulated BV2 Microglial Cells

  • Wonmin Ko
  • Jin-Soo Park
  • Kwan-Woo Kim
  • Jongwon Kim
  • Youn-Chul Kim
  • Hyuncheol Oh
ORIGINAL ARTICLE

Abstract

Four nardosinone-type sesquiterpenes, nardosinone, isonardosinone, kanshone E, and kanshone B, were isolated from the hexane fraction of Nardostachys jatamansi (Valerianaceae) methanol extract. The structures of these compounds were mainly established by analyzing the data obtained from nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). In this study, we investigated their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV2 microglial cells. The results showed that nardosinone-type sesquiterpenes inhibited the production of pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-induced BV2 microglial cells. These inhibitory effects were correlated with the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these sesquiterpenes also attenuated the mRNA expression of pro-inflammatory cytokines including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in LPS-induced BV2 microglial cells. During the evaluation of the signaling pathways involved in these anti-neuroinflammatory effects, western blot analysis and DNA-binding activity assay revealed that the suppression of inflammatory reaction by these sesquiterpenes was mediated by the inactivation of nuclear factor-kappa B (NF-κB) pathway. These sesquiterpenes also suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways in LPS-stimulated BV2 microglial cells. Taken together, these four nardosinone-type sesquiterpenes inhibited NF-κB- and MAPK-mediated inflammatory pathways, demonstrating their potential role in the treatment of neuroinflammation conditions.

KEY WORDS

Nardostachys jatamansi sesquiterpene nuclear factor-kappa B (NF-κB) mitogen-activated protein kinase (MAPK) anti-neuroinflammation 

Notes

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2016R1A2B4007472).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Wonmin Ko
    • 1
  • Jin-Soo Park
    • 1
  • Kwan-Woo Kim
    • 1
  • Jongwon Kim
    • 1
  • Youn-Chul Kim
    • 1
  • Hyuncheol Oh
    • 1
  1. 1.College of PharmacyWonkwang UniversityIksanRepublic of Korea

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