Food Science

Three new diarylheptanoids, (4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-4,6-dien-3-one, letestuianin A (1), (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien-3-one, letestuianin B (2), and 1,7-bis(4-hydroxyphenyl)heptan-3,5-dione, letestuianin C (3), as well as the known (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one (5) were isolated from Aframomum letestuianum. The known flavonoids 3-acetoxy-5,7,4′-trihydroxyflavanone, 3-acetoxy-7-methoxy-5,4′-dihydroxyflavanone, 7-methoxy-3,5,4′-trihydroxyflavone, and 3,3′,4′,5,7-pentahydroxyflavan were also obtained from this plant. Their structures were determined using a combination of 1D and 2D NMR techniques. The four diarylheptanoids were tested for growth inhibitory activity in vitro versus bloodstream forms of African trypanosomes. IC 50 values in the range of 1-3 µg/mL were found for compounds 3 and 5.

Glossocalyx brevipes Benth (Monimiaceae) is a shrub with hairy stems and leaves, growing in the humid rain forests of West and Central Africa [1]. In Cameroonian folk medicine, the macerated leaves are added to antifever preparations. A previous phytochemical study reported the isolation of aporphine alkaloids, but these were not tested for antimalarial activity . In a continuation of our search for new anti-plasmodial agents from plant sources [3], the CH 2 Cl 2 /CH 3 OH (1/1) extract of the leaves of G. brevipes, that revealed moderate antiplasmodial activity, was investigated and three homogentisic acid derivatives and two alkaloids were isolated.

Cystic fibrosis (CF) results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel localized at the plasma membrane of diverse epithelia. The most common mutation leading to CF, Delta F508, occurs in the first nucleotide-binding domain (NBD1) of CFTR. The Delta F508 mutation disrupts protein processing, leading to a decreased level of mutant channels at the plasma membrane and reduced transepithelial chloride permeability. Partial correction of the Delta F508 molecular defect in vitro is achieved by incubation of cells with several classes of chemical chaperones, indicating that further investigation of novel small molecules is warranted as a means for producing new therapies for CF. The yeast two-hybrid assay was used to study the effect of CF-causing mutations on the ability of NBD1 to self-associate and form dimers. A yeast strain demonstrating defective growth as a result of impaired NBD1 dimerization due to Delta F508 was used as a drug discovery bioassay for the identification of plant natural product compounds restoring mutant NBD1 interaction. Active compounds were purified and the chemical structures determined. The purified compounds were tested in epithelial cells expressing CFTR Delta F508 and the resulting effect on transepithelial chloride permeability was assessed using short-circuit chloride current measurements. Wild-type NBD1 of CFTR forms homodimers in a yeast two-hybrid assay. CF-causing mutations within NBD1 that result in defective processing of CFTR (Delta F508, Delta I507, and S549R) disrupted NBD1 interaction in yeast. In contrast, a CF-causing mutation that does not impair CFTR processing (G551D) had no effect on NBD1 dimerization. Using the yeast-based assay, we identified a novel limonoid compound (TS3) that corrected the Delta F508 NBD1 dimerization defect in yeast and also increased the chloride permeability of Fisher Rat Thyroid (FRT) cells stably expressing CFTR Delta F508. The establishment of a phenotype for the Delta F508 mutation in the yeast two-hybrid system yielded a simple assay for the identification of small molecules that interact with the mutant NBD1 and restore dimerization. The natural product compound identified using the system (TS3) was found to increase chloride conductance in epithelial cells to an extent comparable to genistein, a known CFTR activator. The yeast system will thus be useful for further identification of compounds with potential for CF drug therapy.

Background & aims: Exposure of parenteral multivitamin preparation (MVP) to light generates peroxides. Light-exposed MVP induces an oxidant stress in lung but not in liver. This discrepancy suggests differences in handling of infused antioxidant vitamins between the two organs. Hypothesis: antioxidant capacity of lung depends on the MVP concentration and light protection of infused solutions. Methods: Protocol 1: four groups of three-day old guinea pigs received the base solution (5% dextrose + 0.45% NaCl) enriched with 0%, 1%, 2% and 3% MVP. Protocol 2: three further groups received the base solution + 2% MVP either light-exposed or light-protected or lightprotected + 300 mM H 2 O 2 . After 4 days, lung and liver were sampled for vitamin determinations. Data were analyzed by ANOVA. Results: In lung, vitamins A-C-E reached a plateau with 1% MVP. In liver, vitamin A and E increased according to their concentration in solutions. Light exposure and added-H 2 O 2 were associated with lower vitamin E in lung and liver. Retinol was higher in lung and lower in liver of animals receiving light-protected compared to light-exposed solutions.