Targeting detoxification pathways: Larvicidal and GST-Inhibitory potentials of essential oils in Culex pipiens

The mosquito Culex pipiens L. (Diptera: Culicidae) is the principal and most widespread vector of the West Nile virus worldwide. Conventional mosquito control heavily relies on synthetic insecticides, which, despite their effectiveness, contribute to resistance development and pose risks to ecosystems. Resistance is frequently associated with target-site mutations and enhanced detoxification mediated by enzymes such as glutathione S-transferases (GSTs). Essential oils (EOs) from clove ( Syzygium aromaticum L.), marjoram ( Origanum majorana L.), and cinnamon ( Cinnamomum zeylanicum L.) represent promising eco-friendly alternatives for mosquito management. This study investigated their larvicidal potential with particular emphasis on GST inhibition in C. pipiens . Molecular docking revealed that limonene, a major EO constituent, exhibited the strongest binding affinity to GST (ΔG = –6.3 ± 0.2 kcal/mol), surpassing the standard inhibitor diethyl maleate. Biochemical assays confirmed significant GST inhibition, while ADMET predictions indicated favorable pharmacokinetic profiles for limonene alongside certain toxicity alerts. These results suggest that EO-derived compounds act through a dual mechanism—direct larvicidal toxicity and disruption of detoxification pathways. Beyond laboratory efficacy, the findings underscore the potential ecological advantages of EOs, including their rapid environmental degradation and reduced risk of bioaccumulation, though further validation under field conditions and non-target safety assessments remains essential. Collectively, this integrative study highlights the potential of clove, marjoram, and cinnamon EOs as sustainable, safer alternatives to synthetic larvicides in mosquito control programs.