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This study was performed to determine the toxicity and possible mechanism of the larvicidal action of honokiol, extracted from  Magnolia denudata  seeds, and its 10 related compounds against third-instar larvae of insecticide-susceptible  Culex pipiens pallens ,  Aedes aegypti , and  Aedes albopictus  and  Anopheles sinensis  resistant to deltamethrin and temephos. Honokiol (LC 50 , 6.13–7.37 mg/L) was highly effective against larvae of all of the four mosquito species, although the toxicity of the compound was lower than that of the synthetic larvicide temephos. Structure–activity relationship analyses indicated that electron donor and/or bulky groups at the  ortho  or  para  positions of the phenol were required for toxicity. Honokiol moderately inhibited acetylcholinesterase and caused a considerable increase in cyclic AMP levels, indicating that it might act on both acetylcholinesterase and octopaminergic receptors. Microscopy analysis clearly indicated that honokiol was mainly targeted to the midgut epithelium and anal gills, resulting in variably dramatic degenerative responses of the midgut through sequential epithelial disorganization. Honokiol did not affect the AeCS1 mRNA expression level in  Ae .  aegypti  larvae, but did enhance expression of the genes encoding vacuolar-type H + -ATPase and aquaporin 4, indicating that it may disturb the Na + , Cl −  and K +  co-transport systems. These results demonstrate that honokiol merits further study as a potential larvicide, with a specific target site, and as a lead molecule for the control of mosquito populations.

Toxicity and possible mechanisms of action of honokiol from Magnolia denudata seeds against four mosquito species