Bioassay-Guided Isolation of Piplartine from Piper purusanum Yunck (Piperaceae) and Evaluation of Its Toxicity Against Aedes aegypti Linnaeus, 1762, Anopheles darlingi Root, 1926 (Culicidae), and Non-Target Animals.

Abstract

Aedes aegypti and Anopheles darlingi are the primary vectors of dengue and malaria in Brazil. Natural products are currently regarded as promising alternatives for their control, offering environmentally friendly solutions for larval management due to their low toxicity to non-target organisms. Thus, Piplartine, isolated for the first time from Piper purusanum, exhibited larvicidal activity against Ae. aegypti and An. darlingi (LC₅₀ of 14.56 and 26.44 μg/mL), occasioned by the overproduction of reactive oxygen and nitrogen species (66.67 ± 7% and 86.33 ± 6%). Furthermore, piplartine enhanced the activity of key detoxifying enzymes, including catalase (87.00 ± 9 and 94.67 ± 9 μmol of H₂O₂ consumed per minute per mg of protein), glutathione S-transferase (76.00 ± 1 and 134.00 ± 1 μmol/min/mg), mixed-function oxidase (26.67 ± 5 and 55.00 ± 1 nmol cti mg⁻¹ protein), α-esterase, and β-esterase (27.67 ± 7 to 46.33 ± 1 nmol cti mg⁻¹ protein). In contrast, piplartine inhibited acetylcholinesterase activity (43.33 ± 7 and 48.00 ± 2 μmol/min/mg) compared to the negative control DMSO (87.33 ± 1 and 146.30 ± 3 μmol/min/mg). It is important to highlight that piplartine showed no lethal effects on non-target aquatic insects, with 100% survival observed at a concentration of 264.4 μg/mL. In contrast, α-cypermethrin demonstrated acute and rapid toxicity to non-target organisms, with only 9.1% survival. These findings highlight piplartine as a promising larvicide with selective toxicity and low environmental impact, suitable for integrated larval management strategies.