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 (LC 50 ) 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 2tridecanone, palmitic acid (hexadecanoic acid), linoleic acid ((Z,Z)-9,12-octadecadienoic acid), sesamin, β-caryophyllene among other compounds identi ed 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 ndings provide an explorative avenue for developing potential mosquito control agents from Z. chalybeum root constituents.

Benzo[<i>c</i>]phenanthridine alkaloids and glycosylated flavonoids from the roots of <i>Zanthoxylum gilletii</i> (Rutaceae)

“…Further chemotaxonomic insights of the study have been deduced from the presence of the other compounds isolated during the current investigation of the roots of Z. gilletii. Unsurpingsly, the lignan sesamin has been isolated during our investigation as one of the major compounds and it has been mainly reported from several species of the genus Zanthoxylum including Z. chalybeum, Z. paracanthum, Z. leprieurii, Z. rigidum, Z. paracanthum, Z. zanthoxyloides, Z. nitidum and Z. heitzii (Andima et al, 2020;Chakthong et al, 2019;Kaigongi et al, 2020;Muema et al, 2021;Oloya et al, 2021;Omosa et al, 2022;Santos et al, 2020;Wangensteen et al, 2016).…”

Chemical Composition, In Vitro Antioxidant Activities, and Inhibitory Effects of the Acetylcholinesterase of Liparis nervosa (Thunb.) Lindl. Essential Oil

“…This compound showed cytotoxicity to human leukemic cells but no cytotoxicity to normal human dermal fibroblast (HDF) cells [36]. Moreover, palmitic acid previously exhibited AChE inhibition and larval toxicity [37,38]. The results of other studies indicate that the third major component, isopropyl palmitate, is a model chemical penetration enhancer in drug release systems [39].…”

Status and Prospects of Botanical Biopesticides in Europe and Mediterranean Countries

“…The effect of azadirachtin on the growth and developmental stages of larvae with interference on ecdysone and juvenile hormone regulation has also been documented in various insects [ 116 ]. Muema et al [ 117 ] suggested that morphological aberrations in mosquito larvae associated with IGRs from Zanthoxylum chalybeum are due to impacts on the ecdysteroid pathway, finally inducing larval retardation.…”