de Oliveira_2025_Plants.(Basel)_14_

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 (LC(50) of 14.56 and 26.44 microg/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 micromol of H(2)O(2) consumed per minute per mg of protein), glutathione S-transferase (76.00 +/- 1 and 134.00 +/- 1 micromol/min/mg), mixed-function oxidase (26.67 +/- 5 and 55.00 +/- 1 nmol cti mg protein), alpha-esterase, and beta-esterase (27.67 +/- 7 to 46.33 +/- 1 nmol cti mg protein). In contrast, piplartine inhibited acetylcholinesterase activity (43.33 +/- 7 and 48.00 +/- 2 micromol/min/mg) compared to the negative control DMSO (87.33 +/- 1 and 146.30 +/- 3 micromol/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 microg/mL. In contrast, alpha-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.