Antioxidant and Antileishmanial Activities, and Evaluation of Acute Oral Toxicity and Genotoxicity of Bixa orellana Leaf Extracts

Herein, we determined the phytochemical profile and antioxidant and antileishmanial activities of aqueous, saline, and hydroethanolic extracts (AE, SE, and HE, respectively) of Bixa orellana leaves. We also examined acute and dermal toxicities, as well as the genotoxicity of prepared extracts. Phytochemical analysis was performed using thin-layer chromatography, phenolic and flavonoid content assessment, and high-performance liquid chromatography (HPLC). Antioxidant activity was evaluated by assaying DPPH and ABTS⁺ radicals, while antileishmanial activity was examined using Leishmania amazonensis promastigotes. Oral acute toxicity and dermal irritation were assayed in mice at 2,000 mg/kg. Micronucleus and comet assays were employed to examine genotoxicity at 2000 mg/kg. Flavonoids, hydrolysable tannins, anthracene derivatives, reducing sugars, and saponins were detected in all extracts, whereas caffeic acid and condensed tannins were detected in AE and SE. Terpenes and steroids were detected only in HE. Based on the HPLC profile, ellagic acid and flavonoids were present in all extracts, which exerted antioxidant activity, with IC₅₀ values ranging from 6.90 to 23.22 µg/mL for DPPH and ABTS⁺. In addition, AE, HE, and SE inhibited the growth of L. amazonensis promastigotes, presenting IC₅₀ values of 1187.07, 697.26, and 496.38 µg/mL, respectively. No signs of toxicity were detected in the acute toxicity assays, and values of mean score irritation indicated the absence of dermal irritants. Moreover, no genotoxicity was noted in the assays performed. In conclusion, B. orellana leaf extracts are sources of antioxidant and antileishmanial agents with a good safety profile in mice, which could be developed as drugs of natural origin.