Bioactive metabolites from the leaves of Withania adpressa.

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.

journal_name

Pharm Biol

journal_title

Pharmaceutical biology

authors

Ben Bakrim W,El Bouzidi L,Nuzillard JM,Cretton S,Saraux N,Monteillier A,Christen P,Cuendet M,Bekkouche K

doi

10.1080/13880209.2018.1499781

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

505-510

issue

1

eissn

1388-0209

issn

1744-5116

journal_volume

56

pub_type

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