Larvicidal activity, oxidative stress, and enzymatic alterations induced by essential oil from Piper cyrtopodon (Miq.) C.DC (Piperaceae) on Aedes aegypti (Culicidae)

Abstract

Dengue, Zika, and chikungunya are mosquito-borne diseases transmitted by Aedes aegypti, with over 13 million dengue cases, 431.223 chikungunya cases, and 44.242 Zika cases reported in the Americas in 2024. The resistance of Ae. aegypti to synthetic insecticides has driven the search for botanical alternatives, such as essential oils (EOs) from Piper species. This study evaluated the EO from Piper cyrtopodon and its main compounds as larvicides, investigating their mechanism of action. The EO, extracted by hydrodistillation (yield: 1.4 ± 0.2 %), contained germacrene D (57.46 %), cadina-1(10),4-diene (10.57 %), and δ-elemene (8.0 %). It showed significant larvicidal activity against Ae. aegypti, with LC₅₀ values ranging from 20.78 to 146.61 μg/mL over 24 and 48 h. Cadina-1(10),4-diene was the most active compound (p < 0.0001). Biochemical analyses revealed oxidative stress in larvae, with increased reactive oxygen species production (11 ± 2 to 26 ± 2 μmol H₂O₂/g), lipid peroxidation (0.54 ± 0.06 to 2.8 ± 0.22 ηmol MDA/g), and protein oxidation (1.62 ± 0.04 to 4.54 ± 0.51 nmol/mg protein) compared to controls (p < 0.0001). Antioxidant enzymes superoxide dismutase (10.33 ± 3 to 28.33 ± 6 mU/mg protein), catalase (1.04 ± 0.09 to 7.08 ± 2.42 mmol H₂O₂/min/mg protein), and glutathione peroxidase (5.40 ± 1.37 to 14.67 ± 1.52 mmol NADPH/min/mL) were altered, suggesting redox imbalance as a toxicity mechanism. These findings highlight the potential of the EO from P. cyrtopodon as a natural alternative for Ae. aegypti control.