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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.
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https://hal.univ-reims.fr/hal-01992872
Contributor : Jean-Marc Nuzillard Connect in order to contact the contributor
Submitted on : Friday, September 10, 2021 - 2:49:57 PM
Last modification on : Friday, March 18, 2022 - 4:30:04 PM

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Widad Ben Bakrim, Laila El Bouzidi, Jean-Marc Nuzillard, Sylvian Cretton, Noémie Saraux, et al.. Bioactive metabolites from the leaves of Withania adpressa. Pharmaceutical biology, Taylor & Francis, 2018, 56 (1), pp.505-510. ⟨10.1080/13880209.2018.1499781⟩. ⟨hal-01992872⟩

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