Fracionamento fitoquímico biodirecionado pela atividade antirretroviral e avaliação da atividade antioxidante da espécie Lafoensia pacari A.Saint.-Hillaire

Abstract

In recent years, interest in plants with antiviral action has grown exponentially and some have been reported to have anti-HIV properties. The human immunodeficiency virus (HIV) is responsible for the pathological basis of the acquired immunodeficiency syndrome (AIDS) being one of the greatest challenges for public health. The importance of proving the anti-reverse transcriptase action of the species Lafoensia pacari A. St.-Hil is justified. (Lythraceae) to identify the substances involved in this action. L. pacari A. St.-Hil. is an endemic plant of the Brazilian cerrado, popularly known as pacarí, foxglove and magava-brava. Within this context, the importance of promoting isolation biodirected by the antiretroviral and antioxidant activity of the species L. pacari is emphasized. This research had as general objective to carry out the phytochemical fractionation bi-directed by the antiretroviral activity and evaluation of the antioxidant activity of the species L. pacari. This is an experimental study in vitro and the methodology involves preparing the plant material, obtaining the ethanolic extract, fractionation, purification, identification and quantification of fractions, acid-base extraction, tests of antioxidant activity, identification and quantification of phenolic compounds from L. pacari fractions and subfractions, nuclear magnetic resonance, HIV-1 reverse transcriptase (RT) inhibition test and molecular docking studies. A systematic review with meta-analysis on the use of medicinal plants, herbal medicines and / or phytopharmaceuticals associated or not with antiretroviral therapy, using the CD4+ T lymphocyte count as the primary variable. It was verified with the meta-analysis that there were no statistically significant differences between the intervention groups and placebo, included in the research, in relation to any of the variables examined in the CD4+ count. From the bio-directed fractionation by antiretroviral activity, there was a greater activity in acetanolic subfractions with emphasis on neutral acetanolic subfraction with 60.98% inhibition of TR and ellagic acid with 88.61% inhibition of TR and and absence of cytotoxicity. It was verified with the cytotoxicity test in macrophage lineage that the chloroform fraction was more toxic than the acetanolic fraction. The analysis of the J-resolved spectrum in the aromatic region showed a simplet at 7.48 and 6.93 ppm, which were identified as ellagic acid and gallic acid respectively. The enzyme 5TIQ obtained a better affinity parameter with the ellagic acid ligand that was confirmed by the HSQC-1H-13C spectra. Gallic acid was also favorable to form interaction with the enzyme 5TIQ, being confirmed through the HSQC-1H-13C spectrum. Through the evaluation of PreADMET it was found that ellagic acid is a promising molecule due to its activity of inhibiting TR and pharmacokinetic parameters and toxicity. The sample Acetanolic subfraction washing acidic compounds showed the best performance in the analyzed variables, with the best results for phenolic compounds, flavonoids and ABTS. The basic wash water acetate subfraction sample showed the worst performance. The variables that most contributed to differentiate the samples in three groups were the phenolic compounds (29.40%) flavonoids (27.90%) and DPPH (22.10%). Chromatographic analysis of the samples allowed for the first time the identification and quantification of phenolic compounds: gallic acid, catechol, chlorogenic acid, vanylic acid, caffeic acid, vanillin, seringaldehyde, salicylic acid, cumaric acid, coumarin, rutin, quercetin and Kaempferol. It was found that, with the exception of chlorogenic acid, vanillic acid, caffeic acid and coumarin, the samples showed a significant difference for the other variables. It is worth highlighting the performance of the sample L. pacari fraction CHCL3 neutral compounds that presented high mean values for catechol, vanillin, salicylic acid, quercetin and kaempferol. The identification and quantification of phenolic compounds and multivariate analysis in the study of the phenolic composition and antioxidant profile suggest that L. pacari can be promising as an anti-HIV therapeutic agent.