Anti-Inflammatory Effect and Toxicological Profile of Pulp Residue from the Caryocar Brasiliense, a Sustainable Raw Material.

Caryocar brasiliense Cambess is a plant species typical of the Cerrado, a Brazilian biome. The fruit of this species is popularly known as pequi, and its oil is used in traditional medicine. However, an important factor hindering the use of pequi oil is its low yield when extracted from the pulp of this fruit. Therefore, in this study, with aim of developing a new herbal medicine, we an-alyzed the toxicity and anti-inflammatory activity of an extract of pequi pulp residue (EPPR), fol-lowing the mechanical extraction of the oil from its pulp. For this purpose, EPPR was prepared and encapsulated in chitosan. The nanoparticles were analyzed, and the cytotoxicity of the encapsu-lated EPPR was evaluated in vitro. After confirming the cytotoxicity of the encapsulated EPPR, the following evaluations were performed with non-encapsulated EPPR: in vitro anti-inflammatory activity, quantification of cytokines, and acute toxicity in vivo. Once the anti-inflammatory activity and absence of toxicity of EPPR were verified, a gel formulation of EPPR was developed for topical use and analyzed for its in vivo anti-inflammatory potential, ocular toxicity, and previous stability assessment. EPPR and the gel containing EPPR showed effective anti-inflammatory activity and lack of toxicity. The formulation was stable. Thus, a new herbal medicine with anti-inflammatory activity can be developed from discarded pequi residue.

Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations.

In the present study, a series of chalcones and their B-aryl analogues were prepared and evaluate as inhibitors of myeloperoxidase (MPO) chlorinating activity, using in vitro and ex vivo assays. Among these, B-thiophenyl chalcone (analogue 9) demonstrated inhibition of in vitro and ex vivo MPO chlorinating activity, exhibiting IC50 value of 0.53 and 19.2 µM, respectively. Potent ex vivo MPO inhibitors 5, 8 and 9 were not toxic to human neutrophils at 50 µM, as well as displayed weak 2,2-diphenyl-1-pycrylhydrazyl radical (DPPH•) and hypochlorous acid (HOCl) scavenger abilities. Docking simulations indicated binding mode of MPO inhibitors, evidencing hydrogen bonds between the amino group at 4'position (ring A) of chalcones with Gln91, Asp94, and Hys95 MPO residues. In this regard, the efficacy and low toxicity promoted aminochalcones and arylic analogues to the rank of hit compounds in the search for new non-steroidal anti-inflammatory compounds.

Ligand screening assay for the enzyme kallikrein immobilized on NHS-activated Sepharose.

Human tissue kallikreins (KLKs) are serine proteases involved in various physiological and pathological conditions, including cancer and neurological disorders. These enzymes constitute attractive drug targets, which has stimulated the search for new KLK inhibitors. In this study, we have covalently immobilized porcine pancreas KLK on an NHS-activated Sepharose matrix, to obtain KLK-Sepharose-NHS. The immobilized enzyme showed high recovered activity and maintained the ability of free KLK to recognize the synthetic substrate Z-Phe-Arg-AMC (KMapp = 10.3 ±â€¯0.9 µM). As proof of concept, we used leupeptin as a reference inhibitor to perform inhibition studies for KLK-Sepharose-NHS and to determine the half-maximal inhibitory concentration (IC50 = 0.13 ±â€¯0.01 µM), the inhibition constant (Ki = 0.06 µM), and the leupeptin inhibition mechanism. We evaluated several complex matrixes (plant crude extract) by the same bioassay, to demonstrate their applicability. The species Solanum lycocarpum, Stryphnodendron adstringens, and Psychotria carthagenensis gave the best results. KLK-Sepharose-NHS was fully active after six consecutive reaction cycles and retained about 60 % of its initial activity after being used for at least five months, so the bioassay developed herein is a promising strategy to screen and to identify KLK ligands.

The Combination of Vitamin K3 and Vitamin C Has Synergic Activity against Forms of Trypanosoma cruzi through a Redox Imbalance Process.

Chagas' disease is an infection that is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. Because of severe side effects and variable efficacy, the current treatments for Chagas' disease are unsatisfactory, making the search for new chemotherapeutic agents essential. Previous studies have reported various biological activities of naphthoquinones, such as the trypanocidal and antitumor activity of vitamin K3. The combination of this vitamin with vitamin C exerted better effects against various cancer cells than when used alone. These effects have been attributed to an increase in reactive oxygen species generation. In the present study, we evaluated the activity of vitamin K3 and vitamin C, alone and in combination, against T. cruzi. The vitamin K3 + vitamin C combination exerted synergistic effects against three forms of T. cruzi, leading to morphological, ultrastructural, and functional changes by producing reactive species, decreasing reduced thiol groups, altering the cell cycle, causing lipid peroxidation, and forming autophagic vacuoles. Our hypothesis is that the vitamin K3 + vitamin C combination induces oxidative imbalance in T. cruzi, probably started by a redox cycling process that leads to parasite cell death.