Tetrahydrohyperforin and Octahydrohyperforin Are Two New Potent Inhibitors of Angiogenesis

We have previously shown that hyperforin, a phloroglucinol derivative found in St. John's wort, behaves as a potent anti-angiogenic compound. To identify the reactive group(s) mainly involved in this anti-angiogenic effect, we have investigated the anti-angiogenic properties of a series of stable derivatives obtained by oxidative modification of the natural product. In addition, in the present work we have studied the role of the four carbonyl groups present in hyperforin by investigating the potential of some other chemically stable derivatives.The experimental procedures included the analysis of the effects of treatment of endothelial cells with these compounds in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Our study with hyperforin and eight derivatives shows that the enolized beta-dicarbonyl system contained in the structure of hyperforin has a dominant role in its antiangiogenic activity. On the other hand, two of the tested hyperforin derivatives, namely, tetrahydrohyperforin and octahydrohyperforin, behave as potent inhibitors of angiogenesis. Additional characterization of these compounds included a cell specificity study of their effects on cell growth, as well as the in vivo Matrigel plug assay.These observations could be useful for the rational design and chemical synthesis of more effective hyperforin derivatives as anti-angiogenic drugs. Altogether, the results indicate that octahydrohyperforin is a more specific and slightly more potent antiangiogenic compound than hyperforin

Synthesis of polylactic acid initiated through biobased antioxidants: Towards intrinsically active food packaging

Polylactide (PLA)-based polymers, functionalized with biobased antioxidants, were synthesized, to develop an intrinsically active, biobased and potentially biodegradable material for food packaging applications. To achieve this result, phenolic antioxidants were exploited as initiators in the ring opening polymerization of l-lactide. The molecular weight, thermal properties and in vitro radical scavenging activity of the polymers obtained were compared with the ones of a PLA Natureworks 4043D, commonly used for flexible food packaging applications. The most promising synthesized polymer, bearing vanillyl alcohol as initiator (PLA-VA), was evaluated for active food packaging applications. Packaging with PLA-VA films reduced color and fat oxidation of salami during its shelf life.info:eu-repo/semantics/publishedVersio

Pectin-Based Formulations for Controlled Release of an Ellagic Acid Salt with High Solubility Profile in Physiological Media

Among bioactive phytochemicals, ellagic acid (EA) is one of the most controversial because its high antioxidant and cancer-preventing effects are strongly inhibited by low gastrointestinal absorption and rapid excretion. Strategies toward an increase of solubility in water and bioavailability, while preserving its structural integrity and warranting its controlled release at the physiological targets, are therefore largely pursued. In this work, EA lysine salt at 1:4 molar ratio (EALYS), exhibiting a more than 400 times increase of water solubility with respect to literature reports, was incorporated at 10% in low methoxylated (LM) and high methoxylated (HM) pectin films. The release of EA in PBS at pH 7.4 from both film preparations was comparable and reached 15% of the loaded compound over 2 h. Under simulated gastric conditions, release of EA from HM and LM pectin films was minimal at gastric pH, whereas higher concentrations-up to 300 μM, corresponding to ca. 50% of the overall content-were obtained in the case of the HM pectin film after 2 h incubation at the slightly alkaline pH of small intestine environment, with the enzyme and bile salt components enhancing the release. EALYS pectin films showed a good prebiotic activity as evaluated by determination of short chain fatty acids (SCFAs) levels following microbial fermentation, with a low but significant increase of the effects produced by the pectins themselves. Overall, these results highlight pectin films loaded with EALYS salt as a promising formulation to improve administration and controlled release of the compound.This research was funded by the European Union’s Horizon 2020 research and innovation program through the Stance4Health project (Grant No. 816303).Ye

The reaction of hyperforin with hydride reducing agents.

As part of a study aimed at generating analogues of hyperforin (1), the reaction of this prenylated phloroglucinol with various hydride reducing agents was investigated. Hyperforin contains two beta-dicarbonyl systems, one of which is non-enolizable, and it was interesting to assess the relative reactivity of these structural elements in the highly compact framework of the natural product. Depending on the reducing agent employed, a surprising range of compounds could be obtained, sometimes in synthetically useful yields. The stereochemistry of the LiAlH4-reduced product was secured by X-ray analysis and served as a base for elucidating the configuration of a series of reduced and deoxygenated analogues obtained with other reducing agents. The chemoselectivity observed in these reactions is apparently the result of a combination of metal-chelation and hydrogen-bonding effects