Tyrosinase is a key enzyme in melanin synthesis and widely distributed in plants and animals tissues. In mammals, this enzyme is related to pigment production, involved in wound healing, primary immune response and it can also contribute to catecholamines synthesis in the brain. Consequently, tyrosinase enzyme represents an attractive and selective target in the field of the medicine, cosmetics and bio-insecticides. In this paper, experimental kinetics and computational analysis were used to study the inhibition of tyrosinase by analogous of Kojic acid. The main interactions occurring between inhibitors-tyrosinase complexes and the influence of divalent cation (Cu²⁺) in enzymatic inhibition were investigated by using molecular docking, molecular dynamic simulations and electrostatic binding free energy by using the Linear Interaction Energy (LIE) method. The results showed that the electrostatic binding free energy are correlated with values of constant inhibition (r² = 0.97).Thus, the model obtained here could contribute to future studies of this important system and, therefore, eventually facilitate development of tyrosinase inhibitors.

Kojic acid (KA) is a fungal metabolite used as a topical treatment skin-whitening cosmetic agent for melasma in humans; however its potential as an anti-leishmanial agent is unknown. Chemotherapy is one of the most effective treatments for Leishmaniasis. However, the drugs available are expensive, invasive, require long-term treatment and have severe side effects. Thus, the development of new effective leishmanicidal agents is a necessity. In this study we investigated the anti-leishmanial effect of KA on L. amazonensis, following in vitro and in vivo infections. KA (50 μg/mL) was found to decrease the growth by 62% (IC₅₀ 34 μg/mL) and 79% (IC₅₀ 27.84 μg/mL) of promastigotes and amastigotes in vitro, respectively. Ultrastructural analysis of KA-treated amastigotes showed the presence of vesicles bodies into the flagellar pocket, and an intense intracellular vacuolization and swelling of the mitochondrion. During the in vitro interaction of parasites and the host cell, KA reverses the superoxide anions (O₂^-) inhibitory mechanism promoted by parasite. In addition, 4 weeks after KA-topical formulation treatment of infected animals, a healing process was observed with a high production of collagen fibers and a decrease in parasite burden. Thus, these results demonstrated the great potential of KA as an anti-leishmanial compound.

Leishmaniasis is an infectious disease caused by various species of the protozoan parasites of the Leishmania genus and transmitted by phlebotomine sandflies. The protozoa multiply in phagocytic cells, mainly macrophages, which play an important role defending the organism from pathogens. The most effective treatment for leishmaniasis is the chemotherapy and besides the high cost, these drugs are toxic and require a long period of treatment. Currently, some herbal products are considered an important alternative source of a new leishmanicidal agent, which includes the plant Physalis angulata, . We evaluated effects of an aqueous extract from roots of Physalis angulata (AEPa) on Leishmania proliferation, morphology and also determined whether physalins were present in the extract contributing to the knowledge of its pharmacological efficacy. Morphological alterations were determined by light microscopy, transmission and scanning electron microscopy. Host cell viability was evaluated by MTT, and propidium iodide. AEPa were submitted in full HRESITOF analysis. AEPa promoted a dose-dependent reduction on promastigotes (IC50 = 39.5 μg/mL ± 5.1) and amastigotes (IC50 = 43.4 μg/mL ± 10.1) growth. This growth inhibition was associated with several morphological alterations observed in promastigote forms. No cytotoxic effect in mammalian cells was detected (IC50 > 4000 μg/mL). Furthemore, the presence of physalins A, B, D, E, F, G and H were described, for the first time, in the P. angulata root. Results demonstrate that AEPa effectively promotes antileishmanial activity with several important morphological alterations and has no cytotoxic effects on host cells.

Hydrogels consist of a network of highly porous polymeric chains with the potential for use as a wound dressing. Propolis is a natural product with several biological properties including anti-inflammatory, antibacterial and antioxidant activities. This study was aimed at synthesizing and characterizing a polyacrylamide/methylcellulose hydrogel containing propolis as an active ingredient, to serve as a wound dressing alternative, for the treatment of skin lesions. The hydrogels were prepared using free radical polymerization, and were characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetry, differential scanning calorimetry, swelling capacity, mechanical and rheological properties, UV-Vis spectroscopy, antioxidant activity by the DPPH, ABTS and FRAP assays and biocompatibility determined in Vero cells and J774 macrophages by the MTT assay. Hydrogels showed a porous and foliaceous structure with a well-defined network, a good ability to absorb water and aqueous solutions simulating body fluids as well as desirable mechanical properties and pseudoplastic behavior. In hydrogels containing 1.0 and 2.5% propolis, the contents of total polyphenols were 24.74 ± 1.71 mg GAE/g and 32.10 ± 1.01 mg GAE/g and those of total flavonoids 8.01 ± 0.99 mg QE/g and 13.81 ± 0.71 mg QE/g, respectively, in addition to good antioxidant activity determined with all three methods used. Therefore, hydrogels containing propolis extract, may serve as a promising alternative wound dressing for the treatment of skin lesions, due to their anti-oxidant properties, low cost and availability.