Immunomodulatory, trypanocide, and antioxidant properties of essential oil fractions of Lippia alba (Verbenaceae).

BACKGROUND: Parasite persistence, exacerbated and sustained immune response, and continuous oxidative stress have been described to contribute to the development of the cardiac manifestations in Chronic Chagas Disease. Nevertheless, there are no efficient therapies to resolve the Trypanosoma cruzi infection and prevent the disease progression. Interestingly, trypanocide, antioxidant, and immunodulatory properties have been reported separately for some major terpenes, as citral (neral plus geranial), limonene, and caryophyllene oxide, presents in essential oils (EO) extracted from two chemotypes (Citral and Carvone) of Lippia alba. The aim of this study was to obtain L. alba essential oil fractions enriched with the aforementioned bioactive terpenes and to evaluate the impact of these therapies on trypanocide, oxidative stress, mitochondrial bioenergetics, genotoxicity, and inflammatory markers on T. cruzi-infected macrophages. METHODS: T. cruzi-infected J774A.1 macrophage were treated with limonene-enriched (ACT1) and citral/caryophyllene oxide-enriched (ACT2) essential oils fractions derived from Carvone and Citral-L. alba chemotypes, respectively. RESULTS: ACT1 (IC50 = 45 ± 1.7 µg/mL) and ACT2 (IC50 = 80 ± 1.9 µg/mL) exhibit similar trypanocidal effects to Benznidazole (BZN) (IC50 = 48 ± 2.5 µg/mL), against amastigotes. Synergistic antiparasitic activity was observed when ACT1 was combined with BZN (∑FIC = 0.52 ± 0.13 µg/mL) or ACT2 (∑FIC = 0.46 ± 1.7 µg/mL). ACT1 also decreased the oxidative stress, mitochondrial metabolism, and genotoxicity of the therapies. The ACT1 + ACT2 and ACT1 + BZN experimental treatments reduced the pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α) and increased the anti-inflammatory cytokines (IL-4 and IL-10). CONCLUSION: Due to its highly trypanocidal and immunomodulatory properties, ACT1 (whether alone or in combination with BZN or ACT2) represents a promising L. alba essential oil fraction for further studies in drug development towards the Chagas disease control.

In vitro antimicrobial effect of chloroaluminum phthalocyanine nanoemulsion on periodontal bacteria.

CONTEXT: Nowadays, complementary therapies are necessary for a major removal of microbial subgingival biofilm in the conventional treatment of periodontitis. Research has suggested the use of photodynamic therapy (PDT) as a promising therapy to manage oral cavity infections. This project proposes a new combination of photosensitizer chloroaluminum phthalocyanine and nanoemulsion as a strategy for improving bioactivity. The main purpose of this in vitro study was to evaluate the antimicrobial activity of nanoemulsion ClAlPc (ClAlPc-NE) on relevant periodontal bacteria before and after PDT. MATERIALS AND METHODS: The phototoxic and antibacterial effect of ClAlPc-NE was evaluated against epithelial cells derived from an African green monkey kidney using the colorimetric method with salt tetrazolium 3-(4.5-dimethylthiazolyl-2)-2.5-Diphenyltetrazolium bromide (Merck) and periodontopathogen bacteria (Porphyromonas gingivalis (ATCC 33277), Aggregatibacter actinomycetemcomitans (ATCC 33384), and Prevotella intermedia (ATCC 25611) using the plate microdilution method according to Tavares et al., 2018, respectively. The light source used for the PDT was a LED laser (400-700 nm); the cells were irradiated for 2 min using 4.83 joules/cm2. RESULTS: Antibacterial effect of NE-PcAlCl against P. intermedia with minimum inhibitory concentration (MIC) 0.63 µM after TFD was determined. In the case of P. gingivalis and A. actinomycetemcomitans, no biological activity was found after PDT (MIC > 20 µM) under-evaluated experimental conditions. On the other hand, the ClAlPc-free and ClAlPc-NE cells were phototoxic on epithelial cells. CONCLUSION: The results helped to identify the potential use of ClAlPc-NE to inhibit the periodontal bacterial and additional studies are being developed.

Semisynthetic eugenol derivatives as antifungal agents against dermatophytes of the genus Trichophyton.

PURPOSE: Eugenol, the main component of clove bud essential oil (Eugenia caryophyllus), has been linked to antimicrobial, anti-inflammatory, insecticidal and immunomodulatory properties. The purpose of this study was to evaluate the antifungal and cytotoxic activity of eugenol, the essential oil of Eugenia caryophyllus, and some semisynthetic derivatives of eugenol against dermatophytes of the genus Trichophyton. METHODOLOGY: We evaluated the antifungal effect of the compounds, determining the minimum inhibitory concentrations (MICs) by the microdilution method and the minimum fungicidal concentrations by cultures from the inhibitions. Additionally, the inhibition of the radial growth of the mycelium of the dermatophyte fungi was tested by poisoned substrate. Cytotoxicity was measured by the colorimetric method on Vero cells. RESULTS: All of the eugenol compounds tested exhibited antifungal properties, showing MICs of 62.5-500 µg ml-1 , determined within three dermatophyte species: Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans. Among these derivatives, methyl isoeugenol, at concentrations of 300 and 100 µg ml-1, was found to completely inhibit (100 %) radial growth of the mycelium of all three species after 20 days of treatment. Additionally, phenotypic variations related to the decrease in pigment production of T. rubrum were observed after treatment with O-ethyl and O-butyl isoeugenol derivatives. Meanwhile, all of the tested (iso)eugenol molecules exhibited moderate toxicity in Vero cells [50 % cytotoxic concentration (the concentration required for a 50 % reduction in cell viability; CC50): 54.06-265.18 µg ml-1 ). CONCLUSION: The results suggest that the semisynthetic eugenol derivatives (SEDs) show promising antifungal activity and selectivity against dermatophyte fungi.