Bioactive metabolites from the leaves of Withania adpressa

• Main Authors: Widad Ben Bakrim (Author), Laila El Bouzidi (Author), Jean-Marc Nuzillard (Author), Sylvian Cretton (Author), Noémie Saraux (Author), Aymeric Monteillier (Author), Philippe Christen (Author), Muriel Cuendet (Author), Khalid Bekkouche (Author)
• Format: Book
• Published: Taylor & Francis Group, 2018-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1388-0209; 1744-5116; 10.1080/13880209.2018.1499781
• Keywords: withanolides; wadpressine; antioxidant activity; nf-κb inhibition; antiproliferative activity; Therapeutics. Pharmacology; RM1-950
• Source: Pharmaceutical Biology, Vol 56, Iss 1, Pp 505-510 (2018)

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.