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

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

doi:10.3389/fphar.2021.703985

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

Front Pharmacol. 2021 Jul 20:12:703985. doi: 10.3389/fphar.2021.703985. eCollection 2021.

Authors

Affiliations

¹ Laboratory of Immunomodulation and Protozoology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
² Laboratory of Natural Products for Public Health, Pharmaceutical Techonology Institute - Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
³ Student on Postgraduate Program in Translational Research in Drugs and Medicines, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
⁴ Electron Microscopy Nucleus, Adolfo Lutz Institute, São Paulo, Brazil.
⁵ Postgraduate in Animal Science, State University of Maranhão, São Luís, Brazil.

Abstract

Acknowledging the need of identifying new compounds for the treatment of leishmaniasis, this study aimed to evaluate, from in vitro trials, the activity of flavones from Arrabidaea chica against L. amazonensis. The chromatographic profiles of the hydroethanolic extract and a flavone-rich fraction (ACFF) from A. chica 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 (1) and apigenin (2), isolated from chromatographic techniques and identified by Nuclear Magnetic Resonance of ¹H and ¹³C, 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 in vitro activity was assayed against promastigotes and intramacrophagic amastigote forms of L. amazonensis. 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-Leishmania assays indicated that the IC₅₀ 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 (IC₅₀ 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 A. chica against L. amazonensis, encouraging further studies.

Keywords: Arrabidaea chica; L. amazonensis; flavonoids; macrophages; nitric oxide; transmission electron microscopy.