Green tea proanthocyanidins cause impairment of hormone-regulated larval development and reproductive fitness via repression of juvenile hormone acid methyltransferase, insulin-like peptide and cytochrome P450 genes in Anopheles gambiae sensu stricto

Abstract

Successful optimization of plant-derived compounds into control of nuisance insects would benefit from scientifically validated targets. However, the close association between the genotypic responses and physiological toxicity effects mediated by these compounds remains underexplored. In this study, we evaluated the sublethal dose effects of proanthocyanidins (PAs) sourced from green tea (Camellia sinensis) on life history traits of Anopheles gambiae (sensu stricto) mosquitoes with an aim to unravel the probable molecular targets. Based on the induced phenotypic effects, genes selected for study targeted juvenile hormone (JH) biosynthesis, signal transduction, oxidative stress response and xenobiotic detoxification in addition to vitellogenesis in females. Our findings suggest that chronic exposure of larval stages (L3/L4) to sublethal dose of 5 ppm dramatically extended larval developmental period for up to 12 days, slowed down pupation rates, induced abnormal larval-pupal intermediates and caused 100% inhibition of adult emergence. Further, females exhibited significant interference of fecundity and egg hatchability relative to controls (p < 0.001). Using reverse transcription quantitative polymerase chain reaction (RT-qPCR), our findings show that PA-treated larvae exhibited significant repression of AgamJHAMT (p < 0.001), AgamILP1 (p < 0.001) and AgamCYP6M2 (p < 0.001) with up-regulation of Hsp70 (p < 0.001). Females exposed as larvae demonstrated down-regulation of AgamVg (p = 0.03), AgamILP1 (p = 0.009), AgamCYP6M2 (p = 0.05) and AgamJHAMT (p = 0.02). Our findings support that C. sinensis proanthocyanidins affect important vectorial capacity components such as mosquito survival rates and reproductive fitness thus could be potentially used for controlling populations of malaria vectors.

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

“…gambiae, F (5,24) = 105.5, p < 0.001; Ae. aegypti, F (5,24) = 314.4, p < 0.001) but slightly higher doses were required to match the activity of neem oil that was included as positive control. However, the variation in susceptibility to ZCE toxicity was insigni cant (F (1,48) = 0.836, p = 0.365).…”

“…aegypti obtained from a mosquito culture maintained at the International Centre of Insect Physiology and Ecology (icipe), Nairobi. The insects were maintained as previously described [5] at a density of 200 larvae per 1 L of dechlorinated water under controlled insectarium conditions: temperature 30 ± 2˚C, 60-80% relative humidity (RH), and 12-h light/dark cycles.…”

“…Conversely, detailed molecular toxicity studies to demystify the mechanisms of action of various mosquitocidal agents are few. In a recent study, tea proanthocyanidins interfered with mosquito larval growth and reproduction tness by physiologically disrupting the juvenile hormone biosynthetic pathway [5]. Using a yeast two-hybrid reporter system, Lee et al showed that juvenile hormone mimics derived from Lindera erythrocarpa (Lauraceae) and Solidago serotina (Asteraceae) effectively antagonized mosquito juvenile hormone receptor, methoprene-tolerant (Met); killing mosquito larvae and retarding follicle development in the ovaries [6].…”

Phytomediated stress modulates antioxidant status, induces overexpression of CYP6M2, Hsp70, α-esterase, and suppresses the ABC transporter in Anopheles gambiae (sensu stricto) exposed to Ocimum tenuiflorum extracts

“…Due to the challenges associated with the use of synthetic chemicals, the use of eco-friendly and conveniently accessible plant-based alternatives has recently been proposed as a replacement [ 39 ]. Secondary metabolites found in natural products derived from plant extracts have already been shown to induce stress, alter larval development, and delay adult emergence [ 18 , 24 ]. However, there is still a lack of understanding of the toxicity mechanisms of these plant extracts, particularly at the molecular level, which has limited their potential for absolute exploration as ecofriendly plant-based alternatives.…”

“…tenuiflorum had a moderate larvicidal and adulticidal effect on Culex gelidus and Culex quinquefasciatus . Other studies have found that plant extracts cause toxicity by extending larval development, reducing pupation and subsequent adult emergence rates, and decreasing egg output [ 18 , 40 , 41 ].…”