Bioprospecção de plantas medicinais do cerrado maranhense com propriedades antioxidante, antibacteriana contra Corynebacterium spp e toxicidade: aporte para o desenvolvimento de novos medicamentos

Abstract

Corynebacterium diphtheriae is an emerging pathogen, and causes diphtheria, a disease that is related to the production of diphtheria toxin, already presented resistance to several antibiotics, including those used in treatment. In view of this context, the present work had the objective of performing chemical analysis and the study of the antioxidant and toxic activities of medicinal plants of the Maranhão savannah and the influence on the biological properties of Corynebacterium spp. The leaves of 8 medicinal plants were collected in Estreito-MA in July 2014 and submitted to drying. Exsicates were prepared and deposited for identification in the Seabra Attic Herbarium of the Federal University of Maranhão. Hydroalcoholic crude extracts (HCE) were obtained from dry leaves after maceration with 70% ethanol, at the ratio of 1:10, for 7 days, under daily agitation. The HCE were submitted to chemical analysis by high performance liquid chromatography, the determination of minerals by atomic absorption spectrophotometry and the tests for the detection of secondary metabolites, in addition to the quantification of total polyphenols and flavanoids. It was evaluated the antioxidant activity (2,2-diphenyl-1-picryl-hydrazila [DPPH], phosphomolybdenum and ferrous ion reduction) and antibacterial activity by agar diffusion and microdilution to determine the minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of HCE against 14 samples of C. diphtheriae, 1 of Corynebacterium ulcerans and 1 of Corynebacterium pseudodiphtheriticum, also verified the interaction of HCE with 6 antibacterial drugs and the inhibition and eradication of biofilm on the surface of polystyrene. In vitro toxicity (hemolysis and Vero cells) and in vivo (Artemia salina and Tenebrio molitor) was also analyzed. Some plant species showed the catechin, naringenin, rutin, quercetin and apigenin compounds and the classes of secondary metabolites, phenols, tannins, flavanoids, triterpenes, steroids, alkaloids, saponins and coumarins. The main minerals present in the plants were calcium and sodium. Lafoensia pacari presented the highest levels of flavanoids (6.264±0.264mg/g) and total polyphenols (65.33±0.477mg/g) and antioxidant activity with an effective concentration (EC50) of 8.258μg/mL±0.851 for the DPPH method. However, L. pacari showed the highest inhibition halo (64mm) observed for C. diphtheriae and the best MIC (0.002mg/mL) and MBC (15.94mg/mL) for C. diphtheriae and C. ulcerans. The cephalothin drug was the antibacterial that most interacted synergistically with the HCE, being these of Tithonia diversifolia, Anacardium occidentale, Psidium guajava and Passiflora edulis. The plants had the ability to inhibit the formation of biofilms of at least two bacterial samples, mainly of ATCC 27010, ATCC 27012 and CDC KC279, in addition, this last bacterial sample was most influenced by the extracts in biofilm eradication. The lowest cytotoxic concentration (CC50) on Vero cells was 112.8±0.06572μg/mL for T. diversifolia, hemolytic activity (EC50 41.36±0.06187μg/mL) and lethal concentration against A. salina (LC50 129.97±3.8) for L. pacari. The lowest survival rate of T. molitor was 50.56% when injecting the HCE of P. edulis. Thus, it is observed that the studied plant species presented properties that can stimulate and direct the development of new drugs safer and more efficient