Neurotoxic Zanthoxylum chalybeum root constituents invoke mosquito larval growth retardation through ecdysteroidogenic CYP450s transcriptional perturbations

Abstract

Background: Intracellular effects exerted by phytochemicals eliciting insect growth-reducing responses during vector control intervention remain largely underexplored. We studied the effects of Zanthoxylum chalybeum Engl. (Rutaceae) (ZCE) root derivatives against malaria (Anopheles gambiae) and arbovirus vector (Aedes aegypti) larvae to decipher possible molecular targets. Results: We report dose-dependent biphasic effects on larval response, with transient exposure to ZCE and its bioactive fraction (ZCFr.5) inhibiting acetylcholinesterase (AChE) activity, inducing larval lethality and growth retardation at sublethal doses. Half-maximal lethal concentrations (LC50) for ZCE and ZCFr.5 against An. gambiae and Ae. aegypti larvae after 24-h exposure were 9.00 ppm, 12.26 ppm, and 1.58 ppm, 3.21 ppm, respectively. Inhibition of AChE was potentially linked to larval toxicity afforded by 2-tridecanone, palmitic acid (hexadecanoic acid), linoleic acid ((Z,Z)-9,12-octadecadienoic acid), sesamin, β-caryophyllene among other compounds identified in the bioactive fraction. In addition, the phenotypic larval retardation induced by ZCE root constituents were exerted through transcriptional modulation of ecdysteroidogenic CYP450 genes. Conclusion: Collectively, these findings provide an explorative avenue for developing potential mosquito control agents from Z. chalybeum root constituents.