Cycloolivil Isolated from Nardostachys jatamansi Inhibits TNF-α/IFN-γ-Induced Chemokine Production by Blocking NF-κB and JAK/STAT Activation in HaCaT Keratinocytes

Int J Mol Sci. 2024 Mar 15;25(6):3342. doi: 10.3390/ijms25063342.

Abstract

Nardostachys jatamansi is widely used as a traditional medicine in Asian countries. Numerous recent studies have reported the biological activities of its secondary metabolites and extracts. In this study, a total of 14 components were isolated, including cycloolivil and 2-(3'-hydroxy-5'-ethoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5-carboxylic acid, which were first discovered in N. jatamansi. The isolated compounds were investigated for their anti-inflammatory effects on HaCaT keratinocytes and their potential to alleviate skin inflammation. The results of the screening revealed that cycloolivil and 4β-hydroxy-8β-methoxy-10-methylene-2,9-dioxatricyclo[4.3.1.03,7]decane reduced the production of inflammatory cytokines induced by TNF-α/IFN-γ, such as IL-6, IL-8, and RANTES, in keratinocytes. This study focused on exploring the biological effects of cycloolivil, and the results suggested that cycloolivil inhibits the expression of COX-2 proteins. Further mechanistic evaluations confirmed that the anti-inflammatory effects of cycloolivil were mediated by blockage of the NF-κB and JAK/STAT signaling pathways. These results suggest that cycloolivil isolated from N. jatamansi could be used to treat skin inflammatory diseases.

Keywords: JAK/STAT; NF-κB; Nardostachys jatamansi; anti-skin inflammation; keratinocytes.

MeSH terms

  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Interferon-gamma / metabolism
  • Keratinocytes / metabolism
  • NF-kappa B* / metabolism
  • Nardostachys* / metabolism
  • Phenols*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • cycloolivil
  • Interferon-gamma
  • Anti-Inflammatory Agents
  • Phenols