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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-?B 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-?B 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-?B 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-?B 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.

SUBMITTER: Ben Bakrim W

PROVIDER: S-EPMC6249549 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Bioactive metabolites from the leaves of Withania adpressa.

Ben Bakrim Widad W El Bouzidi Laila L Nuzillard Jean-Marc JM Cretton Sylvian S Saraux Noémie N Monteillier Aymeric A Christen Philippe P Cuendet Muriel M Bekkouche Khalid K

Pharmaceutical biology 20181201 1

<h4>Context</h4>Withania (Solanaceae) species are known to be a rich source of withanolides, which have shown several biological properties.<h4>Objective</h4>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.<h4>Materials and methods</h4>Compounds were obtained from the EtOAc extract of W. adpressa leaves. Structure elucidation was carried out mainly by 1 ...[more]

PMID: 30451050

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Project description:Background: Dendrobium officinale, an endangered Chinese herb, has extensive therapeutic effects and contains bioactive ingredients including a large number of polysaccharides and alkaloids, and minimal flavonoids. Firstly, this study attempts to obtain the protocorm-like bodies of this plant through tissue culture to produce the main secondary metabolites whose distribution in each organelle and protocorm like bodies is analyzed. Then, analysis of the correlation between comparative transcriptome sequence and the metabolite content in different organs enables the discovery of putative genes encoding enzymes involved in the biosynthesis of polysaccharides and alkaloids, and flavonoids. Results: The optimum condition for protocorm-like bodies (PLBs) induction and propagation of D. officinale is established. For protocorm induction, we use the seed as the explant, and the optimum medium formula for PLBs propagation is 1/2 MS + α-NAA 0.5 mg·L-1 +6-BA 1.0 mg·L-1 + 2, 4-D 1.5-2.0 mg·L-1 + potato juice 100 g·L-1. The distribution of polysaccharides, alkaloids and flavonoids in D. officinale organs was clarified. Stems, PLBs and leaves have the highest content of polysaccharides, alkaloids and flavonoids, respectively. PLBs replace organs to produce alkaloids in D. officinale, and naringenin was only produced in stem. Hot water extraction (HWE) method was found outperforming the ultrasound-assisted extraction (UAE) method for polysaccharides from D. officinale. A comparative transcriptome analysis of the protocorm-like bodies and leaves of D. officinale showed genes encoding enzymes involved in polysaccharides, alkaloids and flavonoids biosynthetic pathway were differentially expressed. Putative genes encoding enzymes involved in polysaccharides, alkaloids and flavonoids synthetic pathway were identified. Notably, genes encoding enzymes of strictosidine beta-glucosidase, geissoschizine synthase and vinorine synthase in alkaloids biosynthesis of D. officinale are first reported. Conclusions: Our works, especially the identification of candidate genes encoding enzymes involved in metabolites biosynthesis will help to explore and protect the endangered genetic resources and will also facilitate further analysis of the molecular mechanism of secondary metabolites’ biosynthesis in D. officinale.

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Bioactive metabolites from the leaves of Withania adpressa.

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Bioactive metabolites from the leaves of Withania adpressa.

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