Cecropia pachystachya Trécul: identification, isolation of secondary metabolites, in silico study of toxicological evaluation and interaction with the enzymes 5-LOX and α-1-antitrypsin.

Cecropia pachystachya Tréc., popularly known as embaúba, belongs to the Cecropiaceae family and is used by the native population in the treatment of bronchitis, asthma, high blood pressure, fever, and as a diuretic. The pharmacological actions including anti-inflammatory, antioxidant, cardiotonic and sedative were previously reported. The objective of this study was to (1) isolate and identify bioactive compounds extracted from the ethanolic extract of C. pachystachya roots (ERCP), as well as (2) verify the affinity of these metabolites with the enzymes 5-lipoxygenase (5-LOX) and α-1-antitrypsin through in silico tests. Isolation and/or identification were performed using GC-MS, HPLC, Infrared (IR), and nuclear magnetic resonance (NMR) techniques. After isolation and identification of the active compounds, these substances were subjected to the in silico investigation that proceeded by performing PreADMET simulations and molecular docking calculations. The bioactive compounds identified were 1-(+)-ascorbic acid 2,6-dihexadecanoate, ethyl hexadecanoate, ethyl (9E,12E)-octadec-9,12-dienoate, ethyl (Z)-octadec-9-enoate and ethyl octadecanoate by GC-MS; chlorogenic acid, catechin, epicatechin, syringaldehyde by HPLC; ß-sitosterol, sitostenone, beccaridiol, tormentic acid, lupeol, α- and ß-amyrin by classical chromatography, IR, 1H and 13C NMR techniques. The ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties were determined for each bioactive compound. Tormentic acid demonstrated a greater affinity for 5-LOX enzyme while sitostenone demonstrated a higher affinity for the α-1-antitrypsin enzyme. Our findings demonstrated a diverse range of secondary metabolites isolated from C. pachystachya that showed relevant interactions with the enzymes 5-LOX and α-1-antitrypsin. Thus, "embaúba" may be employed in in vivo experimental studies as a form of alternative treatment for chronic lung diseases.Abbreviations: ADT: Autodock Tools; BBB: Blood-brain barrier; CaCo2: Human colonic adenocarcinoma cells; CC: Classic/open Column; TLC: Thin Layer Chromatography; CD40: Differentiation Cluster 40; CENAUREMN: Centro Nordestino de Aplicação e Uso da Ressonância Magnética Nuclear; GC-MS: Gas Chromatography coupled to mass spectrometry; HPLC: High-Perfomance Liquid Chromatography; CYP2C9, CYP2C19, CYP2D6 and CYP3A4: Cytochrome P450 isoenzymes; COPD: Chronic Obstructive Pulmonary Disease; DRX-500: X-Ray Diffraction - 500; ERCP: Ethanolic extract of the roots of C. pachystachya; FAPEPI: Fundação de Amparo à Pesquisa do Piauí; HIA: Human Intestinal Absorption; IR: Infrared; Ki: Inhibition constant; 5-LOX: 5-Lipoxygenase; mM: miliMolar; nM: nanoMolar; OECD423: acute toxic class method; PDB: Protein Data Bank; P-gP: P-glycoprotein; PM2,5: Small inhalable particles 2,5; PPB: Plasm Protein Binding; PreADMET: Prediction Absorption, Distribution, Metabolization, Excretion and Toxicity; NMR: Nuclear Magnetic Resonance; +S9: with metabolic activation; -S9: no metabolic activation; SisGen: Sistema Nacional de Gestão de Patrimônio Genético e do Conhecimento Tradicional Associado; RT: Retention time; TA100: Ames test with TA100 cells line; TA1535: Ames test with cells of the TA1535 cell line; UESPI: State University of Piauí; V79: lung fibroblast cells; ΔG: Gibbs free energy (Kcal/mol); µM: microMolar.

Estudo comparativo da ação do laser GaAlInP e do gerador de alta frequência no tratamento de feridas cutâneas em ratos: estudo experimental / Comparative study of laser action GaAlInP and high-frequency generator in the treatment of skin wounds in rats: an experimental study

Introdução: Na fisioterapia, utilizam-se vários tratamentos para acelerar o processo cicatricial, tais como a radiação com laser e o gerador de alta frequência. Objetivo: Avaliar a ação do laser GaAlInP e do gerador de alta frequência no tratamento de feridas cutâneas. Método: Realizou-se uma ferida cutânea em 24 ratos Wistar, utilizando um punch com 8 mm de diâmetro. Posteriormente, os animais foram divididos em quatro grupos: A, controle; B, laser GaAlInP; C, gerador de alta frequência, e D, laser GaAlInP + gerador de alta frequência, sendo o laser GaAlInP de 670nm, 6 J/cm² e 120 segundos e o gerador de alta frequência com intensidade de 80% e 120 segundos. Resultados: Observou-se relevância significativa (p<0,05) entre os grupos B e C em comparação com o A. Destacou-se o grupo D, em que se obteve p<0,01, pois ele se mostrou expressivamente significativo, quando comparado ao controle. Conclusão: Conclui-se que a terapêutica combinada (laser GaAlInP + gerador de alta frequência) foi eficaz para abreviação do processo cicatrical.

Introduction: Physiotherapy uses various treatments to accelerate the healing process, using laser radiation and high-frequency generator. Objective: To evaluate the action of laser GaAlInP and generator high frequency in the treatment of skin wounds. Methods: We performed a skin wound in 24 rats using a punch with 8 mm diameter. After, the animals were divided into four groups: Group A, control; B, Laser GaAlInP; C, high-frequency generator, and D, Laser GaAlInP + High-Frequency Generator being the GaAlInP laser (670 nm, 6 J/cm², 120/2) and the generator of high frequency (intensity of 80%, 120/2). Results: There was significance (P <0.05) between groups B and C compared with group A, giving emphasis to the group D, which revealed the P <0.01, showing a markedly significant when compared to this control. Conclusion: We conclude that the combination therapy (GaAlInP laser + high-frequency generator) was effective for short cicatrical process.