Mechanistic insights into chlorogenic acid and caffeic acid as novel juvenile hormone antagonists

The search for eco-friendly alternatives to conventional chemical insecticides has intensified due to environmental concerns and pest resistance. Juvenile hormone antagonists (JHANs), which disrupt insect development and reproduction with minimal toxicity to vertebrates, offer a promising avenue for sustainable pest management. In this study, a preliminary screening using a juvenile hormone response region (JHRR)-driven luciferase reporter assay in Drosophila Kc cells found that Polygonum aviculare extract exhibited notable JHAN activity among crude extracts from various plants tested. Guided by literature-reported constituents of P. aviculare, we further identified chlorogenic acid and caffeic acid as potent JHANs. Both compounds inhibited Methoprene-induced JHRR activity and disrupted the interaction between the JH receptor Methoprene-tolerant (Met) and its coactivator Taiman (Tai) in a dose-dependent manner. Mechanistic studies demonstrated that chlorogenic acid and caffeic acid possibly compete with Methoprene for binding to the PAS-B domain of Met, preventing the Methoprene-stimulated association of Met with the chaperone protein Hsp83. This inhibition, in turn, blocks the nuclear translocation of Met and downstream Kr-h1 expression. In vivo assays demonstrated that chlorogenic acid or caffeic acid treatment induced precocious metamorphosis in Ostrinia furnacalis larvae and suppressed ovarian development in adults, mimicking JH depletion. These findings highlight the potential of P. aviculare extracts as a sustainable source of JHANs for integrated pest management, offering a novel mechanism-based approach to reduce reliance on synthetic insecticides.