Bioactive metabolites from the leaves of Withania adpressa

Pharm Biol. 2018 Dec;56(1):505-510. doi: 10.1080/13880209.2018.1499781.

Abstract

Context: Withania (Solanaceae) species are known to be a rich source of withanolides, which have shown several biological properties.

Objective: To identify the compounds responsible for Withania adpressa Coss. antioxidant activity and further test them for their NF-κB inhibition and antiproliferative activity in multiple myeloma cells.

Materials and methods: Compounds were obtained from the EtOAc extract of W. adpressa leaves. Structure elucidation was carried out mainly by 1D- and 2D-NMR, and mass spectrometry. Isolated compounds were tested in a dose-response for their in vitro NF-κB inhibition and antiproliferative activity in multiple myeloma cells after 5 and 72 h treatment, respectively.

Results: The fractionation resulted in the isolation of a new glycowithanolide named wadpressine (5) together with withanolide F, withaferin A, coagulin L, and nicotiflorin. The latter showed a moderate ability to scavenge free radicals in DPPH (IC50 = 35.3 µM) and NO (IC50 = 41.3 µM) assays. Withanolide F and withaferin A exhibited low µM antiproliferative activity against both multiple myeloma cancer stem cells and RPMI 8226 cells. Furthermore, they inhibited NF-κB activity with IC50 values of 1.2 and 0.047 µM, respectively. The other compounds showed a moderate inhibition of cell proliferation in RPMI 8226 cells, but were inactive against cancer stem cells and did not inhibit NF-κB activity.

Discussion and conclusions: One new glycowithanolide and four known compounds were isolated. Biological evaluation data gave further insight on the antitumor potential of withanolides for refractory cancers.

Keywords: NF-κB inhibition; Withanolides; antioxidant activity; antiproliferative activity; wadpressine.

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Cell Proliferation / drug effects
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology
  • HEK293 Cells
  • Humans
  • Multiple Myeloma / drug therapy
  • NF-kappa B / antagonists & inhibitors
  • Phenols / chemistry
  • Phenols / isolation & purification
  • Phenols / pharmacology
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Withania / chemistry*
  • Withanolides / chemistry
  • Withanolides / isolation & purification
  • Withanolides / pharmacology

Substances

  • Antioxidants
  • Flavonoids
  • NF-kappa B
  • Phenols
  • Plant Extracts
  • Withanolides
  • coagulin-L
  • nicotiflorin
  • withaferin A

Grants and funding

The authors are grateful to Centre National de la Recherche Scientifique et Technique (CNRST) in Morocco (URAC35) for financial support.