Phytochemical study, molecular docking, genotoxicity and therapeutic efficacy of the aqueous extract of the stem bark of Ximenia americana L. in the treatment of experimental COPD in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ximenia americana L. is popularly known as yellow plum, brave plum or tallow wood. All the parts of this plant are used in popular medicine. Its reddish and smooth bark are used to treat skin infections, inflammation of the mucous membranes and in the wound healing process. OBJECTIVE: Verification of phytochemical profile, the molecular interaction between flavonoid, (-) epi-catechin and 5-LOX enzyme, by means of in silico study, the genotoxic effect and to investigate the pharmacological action of the aqueous extract of the stem bark of X. americana in pulmonary alterations caused by experimental COPD in Rattus norvegicus. MATERIALS AND METHODS: The identification of secondary metabolites was carried out by TLC and HPLC chromatographic methods, molecular anchoring tests were applied to analyze the interaction of flavonoid present in the extract with the enzyme involved in pulmonary inflammation process and the genotoxic effect was assessed by comet assay and micronucleus test. For induction of COPD, male rats were distributed in seven groups. The control group was exposed only to ambient air and six were subjected to passive smoke inhalations for 20 min/day for 60 days. One of the groups exposed to cigarette smoke did not receive treatment. The others were treated by inhalation with beclomethasone dipropionate (400 mcg/kg) and aqueous and lyophilized extracts of X. americana (500 mg/kg) separately or in combination for a period of 15 days. The structural and inflammatory pulmonary alterations were evaluated by histological examination. Additional morphometric analyses were performed, including the alveolar diameter and the thickness of the right ventricle wall. RESULTS: The results showed that the aqueous extract of the bark of X. americana possesses (-) epi -catechin, in silico studies with 5-LOX indicate that the EpiC ligand showed better affinity parameters than the AracA ligand, which is in accordance with the results obtained in vivo studies. Genotoxity was not observed at the dose tested and the extract was able to stagnate the alveolar enlargement caused by the destruction of the interalveolar septa, attenuation of mucus production and decrease the presence of collagen fibers in the bronchi of animals submitted to cigarette smoke. CONCLUSION: Altogether, the results proved that the aqueous extract of X. americana presents itself as a new option of therapeutic approach in the treatment of COPD.

Determination by chromatography and cytotoxotoxic and oxidative effects of pyriproxyfen and pyridalyl.

Pyriproxyfen (PPF) is a larvicide, used to combat the proliferation of Aedes aegypti larvae. The objective of this study was to analyze the compounds of pyriproxyfen and pyridalyl (PYL) in a commercial larvicide to analyze the cytotoxic and oxidative effects of PPF and PYL. The toxic potential of PPF and PYL were assessed based on lethal concentration (LC50) in Artemia salina, cytotoxicity based on the mitotic index and the chromosomal alterations in Allium cepa and the oxidative damage in Saccharomyces cerevisiae. The PPF and PYL compounds were identified by HPLC-PDA based on their retention times and spectral data. The wavelengths λmax (258 nm) and (271 nm) of the UV spectrum of PYL and PPF and the retention times (RT) (3.38 min) and (4.03 min), respectively. The toxicological potentials of PPF and PYL were significant at concentrations (1, 10, 100 and 1000 ppm), with an LC50 of 48 h (0.5 ppm). PPF and PYL pointed out a cytotoxic effect in A. cepa at all concentrations (0.0001, 0.001, 0.01, 0.1, 1.0, 100 and 1000 ppm), genotoxic effect at concentrations only (0.0001; 0.1; 1; 100 and 1000 ppm), and mutagenic for concentrations (0.1, 100 and 1000 ppm). In relation S. cerevisiae, PPF e PYL prompted oxidative damage at concentrations (100 and 1000 ppm) in all strains (SODWT, Sod1, Sod2, Sod1Sod2, Cat1 and Sod1Cat1). Therefore, the PPF and PYL identificated in commercial larvicide by HPLC-PDA produced cytotoxic and oxidative effects that could cause health and ecosystem risks.