Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities

Abstract

Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of <i>Himatanthus</i><i>drasticus</i>, a plant from the Apocynaceae family. After harvesting, <i>H. drasticus</i> leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. <i>Staphylococcus aureus, Pseudomonas aeruginosa</i>, <i>Listeria monocytogenes</i> and <i>Klebsiella pneumoniae</i> were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against <i>K. pneumoniae</i>. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against <i>K. pneumoniae</i>, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from <i>H. drasticus</i> have antimicrobial and antibiofilm activities against <i>K. pneumoniae</i> and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide.