Isolation of Flavonoids from Deguelia duckeana and Their Effect on Cellular Viability, AMPK, eEF2, eIF2 and eIF4E

Abstract

Preparations of Deguelia duckeana, known in Brazil as timbó, are used by indigenous people to kill fish. Reinvestigation of its extracts resulted in the isolation and identification of 11 known flavonoids identified as 3,5,4'-trimethoxy-4-prenylstilbene (1), 4-methoxyderricidine (2), lonchocarpine (3), 4-hydroxylonchocarpine (4), 4-methoxylonchocarpine (5), 5-hydroxy-4',7-dimethoxy-6-prenylflavanone (6), 4'-hydroxyisolonchocarpine (7), 4'-methoxyisolonchocarpine (8), 3',4',7-trimethoxyflavone (9), 3',4'-methylenedioxy-7-methoxyflavone (10), and 2,2-dimethyl-chromone-5,4'-hydroxy-5'-methoxyflavone (11). Except for 1, 3, and 4 all of these flavonoids have been described for the first time in D. duckeana and the flavanone 6 for the first time in nature. Compounds 2, 3, 4, 7, 9, and 10 were studied for their potential to induce cell death in neuronal SK-N-SH cells. Only the chalcone 4 and the flavanone 7 significantly induced lactate dehydrogenase (LDH) release, which was accompanied by activation of caspase-3 and impairment of energy homeostasis in the MTT assay and may explain the killing effect on fish. Interestingly, the flavone 10 reduced cell metabolism in the MTT assay without inducing cytotoxicity in the LDH assay. Furthermore, the flavonoids 2, 3, 4, 7, and 10 induced phosphorylation of the AMP-activated protein kinase (AMPK) and the eukaryotic elongation factor 2 (eEF2). The initiation factor eIF4E was dephosphorylated in the presence of these compounds. The initiation factor eIF2alpha was not affected. Further studies are needed to elucidate the importance of the observed effects on protein synthesis and potential therapeutic perspectives.

The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation

“…Recent work has identified that 24 h treatment with 50 µM lonchocarpin of SK-N-SH neuroblastoma line induces AMPK phosphorylation, which results in increased glucose uptake and inhibits protein synthesis [27]. Although our data shows effects at lower concentrations, this work corroborates our findings that lonchocarpin decreases cell viability.…”

Establishment of a Cell Suspension Culture of Eysenhardtia platycarpa: Phytochemical Screening of Extracts and Evaluation of Antifungal Activity

“…A mixture of stigmasterol and β -sitosterol isolated from the pericarp of Areca catechu markedly inhibited the spore germination, mycelial growth, and germ-tube elongation of Colletotrichum gloeosporioides [ 53 ]. Studies reported in other species of the Fabaceae family ( Tephrosia apollinea , Dahlstedtia glaziovii , and Deguelia duckeana ), have shown that dichloromethane extracts can inhibit fungal growth because they contain high amounts of flavonoids and prenylated phenolic compounds [ 26 , 54 , 55 ]. Therefore, some plant extracts may be a source of antifungal compounds since they have had to develop compounds to resist infections by fungi present in their environment [ 56 ].…”

Mechanistic insights into dimethyl cardamonin-mediated pharmacological effects: A double control of the AMPK-HMGB1 signaling axis

“…For example, the chalcone phloretin exhibits anticancer effects via AMPK activation [ 64 ]. Other anticancer and/or anti-inflammatory chalcone derivatives have been shown to activate AMPK, such as isoliquiritigenin [ 65 ], 2-bromo-4′-methoxychalcone [ 47 ], the prenylated chalcone xanthohumol [ 66 ], the kava chalcone flavokawain B [ 67 ] and other chalcones [ [68] , [69] , [70] ]. An interesting case is that of licochalcone A which displays antitumor and anti-inflammatory properties, like DMC [ 71 ].…”