Carajurin: a anthocyanidin from Arrabidaea chica as a potential biological marker of antileishmanial activity

• Published in: Biomedicine & pharmacotherapy Vol. 141; p. 111910
• Main Authors: Silva-Silva, João Victor, Moragas-Tellis, Carla J., Chagas, Maria S.S., Souza, Paulo Victor R., Moreira, Davyson L., de Souza, Celeste S.F., Teixeira, Kerolain F., Cenci, Arthur R., de Oliveira, Aldo S., Almeida-Souza, Fernando, Behrens, Maria D., Calabrese, Kátia S.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-09-2021; Elsevier
• Subjects: Animals; Anthocyanins - pharmacology; Antiprotozoal Agents - pharmacology; Leishmania amazonensis; Leishmania mexicana - drug effects; Leishmaniasis, Cutaneous - drug therapy; Macrophages; Macrophages, Peritoneal - drug effects; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Nitric oxide; Nitric oxide synthase; Nitric Oxide Synthase - antagonists & inhibitors; Plant Extracts - pharmacology; Plant Leaves - chemistry; Plants, Medicinal; Nitric oxide synthase; Macrophages; Nitric oxide; Leishmania amazonensis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111910

Leishmaniasis is a group of neglected tropical diseases whose treatment with antimonials bears limitations and has changed little in over 80 years. Medicinal plants have been evaluated as a therapeutic alternative for leishmaniasis. Arrabidaea chica is popularly used as a wound healing and antiparasitic agent, especially as leishmanicidal agent. This study examined the leishmanicidal activity of a crude extract (ACCE), an anthocyanidin-rich fraction (ACAF), and three isolated anthocyanidins from A. chica: carajurin, 3′-hydroxy-carajurone, and carajurone. We evaluated the antileishmanial activity against promastigote and intracellular amastigote forms of Leishmania amazonensis and determined cytotoxicity in BALB/c peritoneal macrophages, as well as nitrite quantification, using the Griess method. Molecular docking was carried out to evaluate interactions of carajurin at the nitric oxide synthase enzyme. All compounds were active against promastigotes after 72 h, with IC50 values of 101.5 ± 0.06 μg/mL for ACCE and 4.976 ± 1.09 μg/mL for ACAF. Anthocyanidins carajurin, 3′-hydroxy-carajurone, and carajurone had IC50 values of 3.66 ± 1.16, 22.70 ± 1.20, and 28.28 ± 0.07 μg/mL, respectively. The cytotoxicity assay after 72 h showed results ranging from 9.640 to 66.74 µg/mL for anthocyanidins. ACAF and carajurin showed selectivity against intracellular amastigote forms (SI> 10), with low cytotoxicity within 24 h, a statistically significant reduction in all infection parameters, and induced nitrite production. Molecular docking studies were developed to understand a possible mechanism of activation of the nitric oxide synthase enzyme, which leads to an increase in the production of nitric oxide observed in the other experiments reported. These results encourage us to suggest carajurin as a biological marker of A. chica.
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•Carajurin is the major anthocyanidin compound of A. chica.•Anthocyanidins are active against promastigote forms of L. amazonensis.•Carajurin is active against intracellular amastigote forms of L. amazonensis.•Carajurin increases nitrite levels in unstimulated or stimulated cells.•Carajurin interacts at the activation site of nitrous oxide synthase.