Blackcurrant press cake by-product: Increased chemical bioaccessibility and reduced antioxidant protection after in vitro simulation of gastrointestinal digestion.

This study describes the bioaccessibility in terms of total phenolic content (TPC) and antioxidant capacity before and after in vitro digestion from blackcurrant press cake extracts (BPC) and the bioactivity in cell culture, human erythrocytes as well as the in silico analysis. Chemical analysis of BPC presented an increase in TPC (270%) and anthocyanins (136%) after in vitro digestion, resulting in an improvement of antioxidant activity (DPPH 112%; FRAP: 153%). This behavior may be related to the highest activity of cyanidin-3-rutinoside, as confirmed by in silico analysis. The digested BPC did not exert cytotoxicity in cells and showed less antioxidant activity against the oxidative damage induced in endothelial cells and human erythrocytes compared to the non-digested extract. The results raise a question about the reliability we should place on results obtained only from crude samples, especially those that will be used to produce foods or nutraceuticals.

Structure-based virtual screening and discovery of New PPARδ/γ dual agonist and PPARδ and γ agonists.

Peroxisome proliferator-activated receptors (PPARs) are involved in the control of carbohydrate and lipid metabolism and are considered important targets to treat diabetes mellitus and metabolic syndrome. The available PPAR ligands have several side effects leading to health risks justifying the search for new bioactive ligands to activate the PPAR subtypes, in special PPARδ, the less studied PPAR isoform. Here, we used a structure-based virtual screening protocol in order to find out new PPAR ligands. From a lead-like subset of purchasable compounds, we identified 5 compounds with potential PPAR affinity and, from preliminary in vitro assays, 4 of them showed promising biological activity. Therefore, from our in silico and in vitro protocols, new PPAR ligands are potential candidates to treat metabolic diseases.

Hologram QSAR studies of antiprotozoal activities of sesquiterpene lactones.

Infectious diseases such as trypanosomiasis and leishmaniasis are considered neglected tropical diseases due the lack for many years of research and development into new drug treatments besides the high incidence of mortality and the lack of current safe and effective drug therapies. Natural products such as sesquiterpene lactones have shown activity against T. brucei and L. donovani, the parasites responsible for these neglected diseases. To evaluate structure activity relationships, HQSAR models were constructed to relate a series of 40 sesquiterpene lactones (STLs) with activity against T. brucei, T. cruzi, L. donovani and P. falciparum and also with their cytotoxicity. All constructed models showed good internal (leave-one-out q2 values ranging from 0.637 to 0.775) and external validation coefficients (r2test values ranging from 0.653 to 0.944). From HQSAR contribution maps, several differences between the most and least potent compounds were found. The fragment contribution of PLS-generated models confirmed the results of previous QSAR studies that the presence of α,ß-unsatured carbonyl groups is fundamental to biological activity. QSAR models for the activity of these compounds against T. cruzi, L. donovani and P. falciparum are reported here for the first time. The constructed HQSAR models are suitable to predict the activity of untested STLs.