Mosquitocidal potential of ricinine from Ricinus communis: An integrative evaluation of larvicidal efficacy, histopathology, non-target toxicity, and in silico mechanism

The development of safe and sustainable mosquito control strategies is critical due to increasing resistance and environmental hazards associated with synthetic insecticides. The present study investigates ricinine, a pyridone alkaloid isolated from Ricinus communis leaves, as a potential mosquito larvicide. Comparative larvicidal evaluation demonstrated enhanced potency from crude extract to purified ricinine, confirming enrichment of the active principle. The bioactive fraction (Fraction 5) from the chloroform extract was purified and identified as ricinine (C 8 H 8 N 2 O 2 ) using FT-IR, 1 H NMR, and 13 C NMR spectral analyses. The compound was more toxic to Cx. quinquefasciatus (LC 50 = 1.466 ppm) than Ae. aegypti (LC 50 = 2.582 ppm), indicating species-specific susceptibility. Ricinine caused pronounced midgut epithelial degeneration, vacuolation, and peritrophic membrane disruption in treated larvae, interfering with digestive and absorptive functions. Molecular docking analysis indicated a potential interaction of ricinine with acetylcholinesterase (AChE1) of Cx. quinquefasciatus , forming hydrogen bonds with ASN43, GLY10, and MET9 and hydrophobic interactions with TYR74, based on in silico predictions. Non-target toxicity assays showed low acute effects on Poecilia reticulata and Diplonychus indicus under laboratory conditions. Collectively, these results demonstrate that ricinine exhibits selective larvicidal activity, pronounced midgut damage, and predicted affinity toward AChE, highlighting its potential as a plant-derived larvicidal candidate. Although ricinine is a known alkaloid, this study provides novelty through integrated evaluation of species-specific larvicidal efficacy, midgut histopathology, non-target toxicity, and predicted molecular interactions with mosquito acetylcholinesterase in a single experimental framework.