New withanolides with anti-inflammatory activity from the leaves of Datura metel L

Bioorg Chem. 2020 Jan:95:103541. doi: 10.1016/j.bioorg.2019.103541. Epub 2019 Dec 28.

Abstract

Twenty three undescribed withanolides, daturmetelides A-W (1-23), were isolated from 70% EtOH extract of the leaves of Datura metel L. The structural characterizations and relative configurations of 1-23 were elucidated by extensive spectroscopic analysis as well as by comparison with literature values. The absolute configurations of 1 and 3 were determined by X-ray crystallography. Bioassay results showed that 1 and 7 exhibited moderate inhibitory effects against NO production in lipopolysaccharide-stimulated RAW 264.7 cells (IC50 values of 13.74 μM and 13.92 μM, respectively). In addition, 1 and 7 showed significant anti-inflammatory activities against the production of TNF-α, IL-1β, IL-6 and COX-2. Western blot analysis was further performed to reveal the mechanism of anti-inflammatory action via inhibition of the NF-κB activation.

Keywords: Anti-inflammatory activity; Datura metel L.; NF-κB; Withanolides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Datura metel / chemistry*
  • Humans
  • Mice
  • Molecular Structure
  • Plant Leaves / chemistry*
  • RAW 264.7 Cells
  • Spectrum Analysis / methods
  • Withanolides / chemistry
  • Withanolides / isolation & purification
  • Withanolides / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Withanolides