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.

Natural withanolides, an update

“…Withaperuvin M ( 204 ) 64 contains an unusual 1,4-dione moiety. A glycowithanolide with a rare 3β- O -(α- l -rhamnopyranosyl-(1-4)-β- d -glucopyranosyl) moiety, named wadpressine ( 205 ), 94 was isolated from the leaves of Withania adpressa . 94 The structure of 15α-acetoxyphysachenolide D ( 206 ) was confirmed by X-ray crystallographic analysis.…”

“…62 2.2.1.2.2 5-Enes with a 17a-side chain. Seventeen 5-ene withanolides with a 17a-side chain (199-215) 32,64,71,76,[93][94][95] were found in the coverage period. Interestingly, all of them possess a 14a,17b,20-trihydroxy-1-one group.…”

Multiple Myeloma Inhibitory Activity of Plant Natural Products

“…The class of terpenoids shows a range of interesting constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells [ 179 ]. The quassinoid bruceantin as well showed low nanomolar IC 50 values in RPMI8226 cells and inhibited MM-CSC in a nanomolar range [ 182 , 183 ], a fact that was also observed for withaferin A and withanolide F [ 185 ]. All three compounds are lactones, but also share the structural feature of a cyclohexenone ring, which might be a crucial functional group for the compounds’ activity.…”

“…Two more triterpene lactones, withaferin A and withanolide F, were isolated from the leaves of Withania adpressa , a Moroccan endemic species and local remedy for the treatment of food intoxication [ 185 ]. Both compounds were found to inhibit proliferation of RPMI8226 and MM-CSC cells, with IC 50 values of 0.2 and 0.3 µM (withaferin A) and 0.1 and 5.3 µM (withanolide F), respectively, after 72 h of incubation.…”

Critical review of the Withania somnifera (L.) Dunal: ethnobotany, pharmacological efficacy, and commercialization significance in Africa

“…Alcoholic extract of the plant leaves constitutes withanolide D, E (Lavie et al 1968 , 1972 ), withanolides F–M (Glotter et al 1973 , 1977 ), withanolides N, O (Ganzera et al 2003 ), and withanolide P (Glotter et al 1977 ). Leaves of the plant extracted with ethanol contain (5R,6S,7S,8S,9S,10R,13S,14S,17S,20R,22R)-6,7α-epoxy-5,17-α,27-trihydroxy-1-oxo-22R-witha-2,24-dienolide (Ben et al 2018 ). Methanolic extract of the plant roots constitutes numerous dragendorff positive alkaloids that are phytochemicals recognized as anaferine, anahygrine, choline, pseudotropine, cuscohygrine, isopelletierine, dl -isopelletierine-3-tropyltigloate, hentriacontane, hygrine, mesoanaferine, somniferine, 3α-tigloyloxtropine, visamine, withanine, withananine, and withasomnine along with ashwagandhine, pyrazole derivatives, and pseudowithanine (Saleem et al 2020 ).…”