Physicochemical characterization and cosmetic applications of Passiflora nitida Kunth leaf extract

Abstract Passiflora nitida Kunth, an Amazonian Passiflora species, is little studied, although the specie's high biological potential. Herein the plant's pharmacognostic characterization, extract production, antioxidant potential evaluation, and application of this extract in cosmetic products is reported. The physical chemical parameters analyzed were particle size by sieve analysis, loss through drying, extractive yield, total ash content, laser granulometry, specific surface area and pore diameter (SBET), differential scanning calorimetry, thermogravimetry (TG), and wave dispersive X-Ray fluorescence (WDXRF). Total phenol/flavonoid content, LC-MS/MS analysis, DPPH and ABTS antioxidant radical assays, cytotoxicity, melanin, and tyrosinase inhibition in melanocytes test provided evidence to determine the content of the major constituent. P. nitida dry extract provided a fine powder with mesopores determined by SBET, with the TG curve showing five stages of mass loss. The antioxidant potential ranged between 23.5-31.5 mg∙mL-1 and tyrosinase inhibition between 400-654 µg∙mL-1. The species presented an antimelanogenic effect and an inhibitory activity of cellular tyrosinase (26.6%) at 25 µg/mL. The LC-MS/MS analysis of the spray-dried extract displayed the main and minor phenolic compounds constituting this sample. The results indicate that P. nitida extract has promising features for the development of cosmetic formulations

Coumaric acid derivatives as tyrosinase inhibitors: Efficacy studies through in silico, in vitro and ex vivo approaches.

p-Coumaric acid is a known inhibitor of tyrosinase, an enzyme involved in the initial steps of the melanin synthesis in human and other species. However, its low lipophilicity impairs its penetration through skin and efficacy as antimelanogenic agent indeed. Accordingly, this paper reports the assessment of several coumaric acid derivatives as tyrosinase inhibitors and antimelanogenic agents in in vitro, in silico and ex vivo assays. The compounds were designed with modifications in the aromatic and acid moieties of p-coumaric acid, being the coumarate esters the most promising derivatives. The compounds showed higher tyrosinase inhibitory activity (pIC50 3.7-4.2) than the parent acid, being compounds 1d, 1e and 1f the most potent inhibitors. Docking analysis showed that these esters are competitive inhibitors per se, and act independently of a redox mechanism as suggested by DPPH assays. Moreover, the esters showed efficacy in reducing the melanin deposition in human skin fragments at 0.1% concentration, especially compound 1e. In summary, there is an important equilibria between tyrosinase affinity and lipophilicity that must be considered to get effective antimelanogenic agents with adequate permeability in the skin.

Coumaric acid analogues inhibit growth and melanin biosynthesis in Cryptococcus neoformans and potentialize amphotericin B antifungal activity.

Fungal infections are on the rise, since the imunocompromised population is increasing due to AIDS/HIV, organ transplant and chemotherapy. Many environmental and pathogenic fungi are able to accomplish melanin biosynthesis as a virulence factor to promote host invasion. Melanized cells are more resistant to radiation, oxidative and osmotic stresses; also melanin confers an advantage in vivo, since melanized cells are more resistant to phagocytic engulfment and oxidative stress caused by the host defense cells and by some antifungal drugs, such as fluconazole (FCZ) and amphotericin B (AmB). Brown, red or black melanin pigments can be produced by the polyketide pathway (DHN-melanin) or from dihydroxyphenols, such as L-DOPA (L-3,4-dihydroxyphenylalanine) and L-tyrosine by polyphenoloxidases. Among several pathogenic fungi, Cryptococcus neoformans is a melanized yeast that causes pneumonia and meningoencephalitis in immunocompromised patients. The knockout of the laccase genes or other interruptions on melanin biosynthetic pathway generates cryptococcal strains with attenuated virulence in an animal model. In this study 16 analogues of coumaric and cinnamic acid were evaluated as possible tyrosinase inhibitors. We have identified some valuable inhibitors of C. neoformans growth and melanin biosynthesis disruption agents. The results showed that coumaric acid derivatives (1a-c), the ketones (3a-b) and 2-allylphenol (7c) are significant inhibitors of tyrosinase and melanization of the fungus. Two analogues (1b and 3b) were selected as promising antimelanogenic agents to be combined with AmB, showing to promote 16-fold reduction in the AmB fungicidal concentration with no appreciable cytotoxicity to mammalian cells. The data suggest that inhibition of the melanin biosynthesis by these compounds may increase the susceptibility of the cells to the oxidative stress generated by AmB. In summary, our data show that C. neoformans can be a suitable model system to test novel inhibitors that target melanin biosynthesis, and novel compounds for adjunct therapy against C. neoformans were identified.

A Tyrosinase Inhibitor from a Nitrogen-Enriched Chemically Engineered Extract.

The enzyme tyrosinase is involved in the biosynthesis of melanin and the enzymatic browning of fruits and vegetables, and therefore, its inhibitors have potential to treat hyperpigmentary disorders or to function as food antibrowning agents. The use of hydrazine monohydrate as a reagent to prepare chemically engineered extracts can lead to semisynthetic compounds that contain the portion N-N, a fragment rarely found in natural products and present in some tyrosinase inhibitors. Here, we report the tyrosinase inhibition screening of a series of chemically engineered extracts that are diversified by reaction with hydrazine. LC-MS was used to evaluate the change in composition produced by the reaction. Bioguided fractionation of the most active chemically engineered extract, prepared from Matricaria recutita L., led to the discovery of a pyrazole that inhibits tyrosinase with an IC50 value of 28.20 ± 1.13 µM. This compound was produced by a one-pot double chemical transformation of its natural precursor, which includes an unexpected selective removal of one -OH group.

Chilean berry Ugni molinae Turcz. fruit and leaves extracts with interesting antioxidant, antimicrobial and tyrosinase inhibitory properties.

The knowledge of the biological properties of fruits and leaves of murta (Ugni molinae Turcz.) has been owned by native Chilean culture. The present study investigated the phenolic content, the antioxidant, antimicrobial and anti-tyrosinase activities of different murta fruit and leaves extracts to approach their uses on future food, pharmaceutical and cosmetic applications. Extractions of murta fruit and leaves were carried out under water, ethanol and ethanol 50%. Phenolic content of these extracts was measured through Folin Ciocalteu test and the antioxidant power by four different antioxidant systems (ORAC, FRAP, DPPH and TEAC assays) owing to elucidate the main mechanism of antioxidant. Some flavonoids, such as rutin, isoquercitrin and quercitrin hydrate were identified and quantified through HPLC analysis. Antimicrobial activity was determined measuring minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) values against Escherichia coli and Listeria monocytogenes, and the effect of these extracts on L. monocytogenes was confirmed by flow cytometry. Highest contents of polyphenol compounds were obtained in hydroalcoholic extracts (28±1mggallicacid/g dry fruit, and 128±6mggallicacid/g dry leaves). The same trend was found for the values of biological properties: hydroalcoholic extracts showed the strongest activities. Leaves presented higher antioxidant, antimicrobial and anti-tyrosinase properties than murta fruit. Highest antioxidant activity values according to ORAC, FRAP, TEAC and DPPH were 80±8mgTrolox/g, 70±2mgTrolox/g, 87±8mgTrolox/g and 110±12mgTrolox/g, respectively, for murta fruit samples, and 280±10mgTrolox/g, 192±4mgTrolox/g, 286±13mgTrolox/g and 361±13mgTrolox/g, respectively, for murta leaves. These activities were confirmed by HPLC analysis that revealed highest presence of analyzed compounds on leaves hydroalcoholic extract. Regarding to antimicrobial analysis, hydroalcoholic leaves extract presented the highest activity presenting the lowest MIC value for L. monocytogenes (0.07mg/mL). This extract also performed the highest anti-tyrosinase activity (CE50 values of 1.6±0.3 (g/L) and 8.9±1.2 (g/L) for leaves and fruit, respectively).