Abstract
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 (LC50, 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.
Highlights
The yellow fever mosquito Aedes aegypti and Asian tiger mosquito Aedes albopictus are both found in tropical and subtropical regions around the world[1]; by contrast, the common Oriental mosquito Anopheles sinensis and common house mosquito Culex pipiens pallens are found in South East Asia[2]
The fractions obtained from solvent partitioning of the methanol extract of M. denudata seeds were tested for larvicidal activity against third-instar larvae of insecticide-susceptible Cx. pipiens pallens and Ae. aegypti (Table 1)
Contact mortality bioassay-guided fractionation of the M. denudata seeds led to the identification of three active compounds through spectroscopic analyses, including electron ionized mass spectrometry (EI-MS) and nuclear magnetic resonance (NMR) spectroscopy
Summary
The yellow fever mosquito Aedes aegypti and Asian tiger mosquito Aedes albopictus are both found in tropical and subtropical regions around the world[1]; by contrast, the common Oriental mosquito Anopheles sinensis and common house mosquito Culex pipiens pallens are found in South East Asia[2]. SMs act at multiple, novel target sites[20,21,22,23,24], thereby reducing the potential for resistance[25,26] Efforts to evaluate these benefits of botanical insecticides have resulted in numerous papers being published annually[27]. No previous studies have investigated the potential use of M. denudata for managing mosquitoes, insecticide-resistant mosquitoes, for future commercialization, as well as the mechanisms of larvicidal action of the plant constituents. The aim of this study was to assess whether the neolignan honokiol; two fatty acids, linoleic acid and palmitic acid, that were extracted from M. denudata seeds; and magnolol, a structural isomer of honokiol, showed contact toxicity against third-instar larvae of insecticide-susceptible laboratory colonies of Cx. pipiens pallens, Ae. aegypti, and Ae. albopictus and laboratory colonies of An. sinensis resistant to deltamethrin and temephos. The possible mechanism underlying the larvicidal actions of the two neolignans against Ae. aegypti was elucidated using biochemical, histologic, and molecular analyses
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