AUTHOR=Silva-Silva João Victor , Moragas-Tellis Carla Junqueira , Chagas Maria do Socorro dos Santos , Souza Paulo Victor Ramos de , Souza Celeste da Silva Freitas de , Hardoim Daiana de Jesus , Taniwaki Noemi Nosomi , Moreira Davyson de Lima , Dutra Behrens Maria , Calabrese Kátia da Silva , Almeida-Souza Fernando 

TITLE=Antileishmanial Activity of Flavones-Rich Fraction From Arrabidaea chica Verlot (Bignoniaceae)

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.703985

DOI=10.3389/fphar.2021.703985

ISSN=1663-9812

ABSTRACT=<p>Acknowledging the need of identifying new compounds for the treatment of leishmaniasis, this study aimed to evaluate, from <italic>in vitro</italic> trials, the activity of flavones from <italic>Arrabidaea chica</italic> against <italic>L. amazonensis</italic>. The chromatographic profiles of the hydroethanolic extract and a flavone-rich fraction (ACFF) from <italic>A. chica</italic> were determined by high-performance liquid chromatography coupled with a diode-array UV-Vis detector (HPLC-DAD-UV) and electrospray ionization mass spectrometry in tandem (LC-ESI-MS-MS). The flavones luteolin (<bold>1</bold>) and apigenin (<bold>2</bold>), isolated from chromatographic techniques and identified by Nuclear Magnetic Resonance of <sup>1</sup>H and <sup>13</sup>C, were also quantified in ACFF, showing 190.7 mg/g and apigenin 12.4 mg/g, respectively. The other flavones were identified by comparing their spectroscopic data with those of the literature. The <italic>in vitro</italic> activity was assayed against promastigotes and intramacrophagic amastigote forms of <italic>L. amazonensis</italic>. Cytotoxicity tests were performed with peritoneal macrophages of BALB/c mice. Nitrite quantification was performed with Griess reagent. Ultrastructural investigations were obtained by transmission electron microscopy. Anti-<italic>Leishmania</italic> assays indicated that the IC<sub>50</sub> values for ACFF, apigenin, and luteolin were obtained at 40.42 ± 0.10 and 31.51 ± 1.13 μg/mL against promastigotes, respectively. ACFF and luteolin have concentration-dependent cytotoxicity. ACFF and luteolin also inhibited the intra-macrophagic parasite (IC<sub>50</sub> 3.575 ± 1.13 and 11.78 ± 1.24 μg/mL, respectively), with a selectivity index of 11.44 for ACFF. Promastigotes exposed to ACFF and luteolin exhibited ultrastructural changes, such as intense cytoplasm vacuolization and mitochondrial swelling. These findings data evidence the antileishmanial action of flavone-rich fractions of <italic>A. chica</italic> against <italic>L. amazonensis</italic>, encouraging further studies.</p>