Identification of plant compounds that disrupt the insect juvenile hormone receptor complex

Insects impact human health through vector-borne diseases and cause major economic losses by damaging crops and stored agricultural products. Insect-specific growth regulators represent attractive control agents because of their safety to the environment and humans. We identified plant compounds that serve as juvenile hormone antagonists (PJHANs). Using the yeast two-hybrid system transformed with the mosquito JH receptor as a reporter system, we demonstrate that PJHANs affect the JH receptor, methoprene-tolerant (Met), by disrupting its complex with CYCLE or FISC, formation of which is required for mediating JH action. We isolated five diterpene secondary metabolites with JH antagonist activity from two plants: Lindera erythrocarpa and Solidago serotina . They are effective in causing mortality of mosquito larvae at relatively low LD ₅₀ values. Topical application of two diterpenes caused reduction in the expression of Met target genes and retardation of follicle development in mosquito ovaries. Hence, the newly discovered PJHANs may lead to development of a new class of safe and effective pesticides. Significance Juvenile hormone (JH) plays key roles in insect development, reproduction, and many other physiological functions. Because JH is specific to insects, it has been investigated for use as pest control. Although compounds that mimic the action of JH (JH analogues/agonists) are efficient, they have a limited scope of application. Development of potent compounds counteracting JH action (JH antagonists) would find a wider range of control applications. However, thus far, such JH antagonists have not been developed. Here, we report on the discovery of potent JH antagonists in plants, which represents an innate resistance mechanism of plants against insect herbivores. These newly discovered plant JH antagonist compounds could be used as the starting material for developing novel insecticides.