Pepper Constituents Enhance the Toxicity and Neurophysiological Effects of Natural Pyrethrins in Insects

Control of resistant mosquito populations may be approached by the development of novel synergists to improve the performance of already commercialized compounds. Extracts of black pepper (Piper nigrum), Cha Plu (Piper sarmentosum), and Sichuan pepper (Zanthoxylum spp.) synergized natural pyrethrins applied topically to Aedes aegypti females. Both black pepper and Sichuan pepper extracts synergized natural pyrethrins over 13-fold. Synergism was also observed directly on the mosquito larval central nervous system (CNS), suggesting this effect is an important contributing factor distinct from that of reduced metabolism. Piperine, from black pepper, and α-hydroxysanshool (α-HS) from Sichuan pepper, synergized natural pyrethrins on susceptible CNS, but only piperine was capable of synergizing natural pyrethrins on the CNS of a pyrethroid-resistant strain of Ae. aegypti, indicating that these molecules may possess slightly different mechanisms of action or binding sensitivities. These results demonstrate that pepper alkamides are capable of enhancing select insecticidal chemistries via target-site synergism, a novel mechanism of synergism that might be important for enhancing future insecticidal formulations.