Abstract :
[en] Background: In the context of malaria elimination, the development of new antimalarial agents with dual activity, targeting both the asexual and sexual stages of Plasmodium falciparum is of paramount importance. The pivotal role of plant-derived natural products in the discovery of antimalarial drugs inspired us to investigate bioactive compounds with dual activity from Croton sylvaticus, a medicinal plant traditionally used to treat malaria. Purpose: This study aims to scientifically validate the traditional medicinal use of C. sylvaticus, particularly for malaria treatment, by analyzing its essential oils (EOs) and evaluating their antiplasmodial activity. Methods: EOs were extracted from the plant's leaves, roots, and trunk bark using hydrodistillation. Their chemical composition was analyzed through gas chromatographymass spectrometry (GC-MS), and their effects were tested in vitro against both asexual and sexual stages of P. falciparum. Results: Results showed that the major constituents identified were viridiflorene (18.13 ± 0.46%) in root EO, (E)-β-caryophyllene (18.40 ± 0.60%) in trunk bark EO, and farnesyl acetone (15.26 ± 0.25%) in leaf EO. Notably, the leaf EO of Cameroonian C. sylvaticus exhibited a distinct and newly described chemotype, characterized by high levels of farnesyl acetone, β-copaene-4-α-ol, β-cadinene, α-humulene, and trans-longipinocarveol. In vitro testing revealed significant antiplasmodial activity against both the asexual and sexual stages of P. falciparum, with trunk bark EO demonstrating the highest potency (IC50: 9.06 ± 2.15 µg/mL for Pf3D7 and 0.56 µg/mL for gametocytes). Caryophyllene oxide (IC50 = 0.48 µg/mL), (E)-β-caryophyllene (IC50 = 1.15 µg/mL), and sclareol (IC50 = 1.30 µg/mL), the major compounds in the trunk bark EO, play a crucial role in the dual antiplasmodial efficacy of the EO extracted from the trunk bark of C. sylvaticus. Conclusion: These findings support the traditional antimalarial use of C. sylvaticus and stimulate further research in this critical field.
