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Neurotoxicity Research

, Volume 35, Issue 1, pp 230–243 | Cite as

Desoxo-narchinol A and Narchinol B Isolated from Nardostachys jatamansi Exert Anti-neuroinflammatory Effects by Up-regulating of Nuclear Transcription Factor Erythroid-2-Related Factor 2/Heme Oxygenase-1 Signaling

  • Kwan-Woo Kim
  • Chi-Su Yoon
  • Youn-Chul Kim
  • Hyuncheol OhEmail author
ORIGINAL ARTICLE

Abstract

We previously reported that desoxo-narchinol A and narchinol B from Nardostachys jatamansi DC (Valerianaceae) inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2), and the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 protein in lipopolysaccharide (LPS)-stimulated BV2 and primary microglial cells. In this study, we aimed to elucidate the molecular mechanism underlying the anti-neuroinflammatory effects of desoxo-narchinol A and narchinol B. These two compounds inhibited the nuclear factor (NF)-κB pathway, by repressing the phosphorylation and degradation of inhibitor kappa B (IκB)-α, nuclear translocation of the p65/p50 heterodimer, and DNA-binding activity of the p65 subunit. Furthermore, both compounds induced heme oxygenase-1 (HO-1) protein expression, which was mediated by the activation of nuclear transcription factor erythroid-2-related factor 2 (Nrf2). Activation of the Nrf2/HO-1 pathway by desoxo-narchinol A was shown to be regulated by increased phosphorylation of p38 and extracellular signal-regulated kinase (ERK), whereas only p38 was involved in narchinol B-induced activation of the Nrf2/HO-1 pathway. In addition, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling was also involved in the activation of HO-1 by desoxo-narchinol A and narchinol B. These compounds also increased the phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine-9 residue, following phosphorylation of Akt. The anti-neuroinflammatory effect of desoxo-narchinol A and narchinol B was partially blocked by a selective HO-1 inhibitor, suggesting that this effect is partly mediated by HO-1 induction. In addition, both compounds also induced HO-1 protein expression in rat-derived primary microglial cells, which was correlated with their anti-neuroinflammatory effects in LPS-stimulated primary microglial cells. In conclusion, desoxo-narchinol A and narchinol B are potential candidates for the development of preventive agents for the regulation of neuroinflammation in neurodegenerative diseases.

Keywords

Nardostachys jatamansi Desoxo-narchinol A Narchinol B Heme oxygenase-1 Nuclear transcription factor erythroid-2-related factor 2 Nuclear factor κB Anti-neuroinflammation 

Notes

Funding

This study 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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Authors and Affiliations

  • Kwan-Woo Kim
    • 1
  • Chi-Su Yoon
    • 1
  • Youn-Chul Kim
    • 1
  • Hyuncheol Oh
    • 1
    Email author
  1. 1.College of PharmacyWonkwang UniversityIksanRepublic of Korea

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