N-Me-trichodermamide B isolated from Penicillium janthinellum, with antioxidant properties through Nrf2-mediated signaling pathway

Bioorg Med Chem. 2017 Dec 15;25(24):6614-6622. doi: 10.1016/j.bmc.2017.10.044. Epub 2017 Oct 31.

Abstract

A new trichodermamide-like alkaloid, N-Me-trichodermamide B (compound 1), was isolated from a marine fungus Penicillium janthinellum HDN13-309. The structure and absolute configuration of compound 1 were determined by extensive NMR analysis and the modified Mosher's method. This new alkaloid exhibited cellular protection from the H2O2-induced oxidative damage, and the mechanism study revealed that this antioxidant activity was regulated through Nrf2-mediated signaling pathway in HaCaT human keratinocytes. In addition, the inhibitor of p38 abrogated compound 1-induced phosphorylation of p38, up-expression of HO-1, and the nuclear localization of Nrf2. As a result, it suggested that this new alkaloid-induced antioxidant signaling pathway might be initiated through activation of p38.

Keywords: HO-1; N-Me-trichodermamide B; Nrf2; Oxidative stress; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dipeptides / chemistry
  • Dipeptides / isolation & purification
  • Dipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • NF-E2-Related Factor 2 / antagonists & inhibitors*
  • NF-E2-Related Factor 2 / metabolism
  • Penicillium / chemistry*
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Dipeptides
  • NF-E2-Related Factor 2
  • trichodermamide B