Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity

Bioorg Med Chem Lett. 2016 Jun 15;26(12):2755-2759. doi: 10.1016/j.bmcl.2016.04.077. Epub 2016 Apr 26.

Abstract

Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7.8μM. In addition, all compounds were evaluated for potential to inhibit tumor necrosis factor-alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) activity with transfected human embryonic kidney cells 293. Compounds 4-7 inhibited TNF-α-induced NF-κB activity with IC50 values in the range of 0.04-5.6μM.

Keywords: Anti-inflammatory activity; Physalis peruviana; Withanolides; X-ray crystallography.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Physalis / chemistry*
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism
  • Withanolides / chemical synthesis
  • Withanolides / chemistry
  • Withanolides / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Withanolides