Way toward “Dietary Pesticides”: Molecular Investigation of Insecticidal Action of Caffeic Acid against Helicoverpa armigera

• Published in: Journal of agricultural and food chemistry Vol. 62; no. 45; pp. 10847 - 10854
• Main Authors: Joshi, R. S, Wagh, T. P, Sharma, N, Mulani, F. A, Sonavane, U, Thulasiram, H. V, Joshi, R, Gupta, V. S, Giri, A. P
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12-11-2014; American Chemical Society, Books and Journals Division
• Subjects: Animals; caffeic acid; Caffeic Acids - chemistry; Caffeic Acids - pharmacology; digestive system; enzyme activity; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - enzymology; gene expression; Helicoverpa armigera; Insect Proteins - antagonists & inhibitors; Insect Proteins - chemistry; Insect Proteins - genetics; Insect Proteins - metabolism; insecticidal properties; Insecticides - chemistry; Insecticides - pharmacology; insects; Larva - drug effects; Larva - enzymology; Larva - genetics; Larva - growth & development; larvae; Moths - drug effects; Moths - enzymology; Moths - genetics; Moths - growth & development; Peptide Hydrolases - chemistry; Peptide Hydrolases - genetics; Peptide Hydrolases - metabolism; pesticide resistance; pesticides; phenol; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; proteinases; screening; Structure-Activity Relationship; structure-activity relationships; protease inhibitor; Helicoverpa armigera; insecticidal activity; Caffeic acid
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf503437r

Bioprospecting of natural molecules is essential to overcome serious environmental issues and pesticide resistance in insects. Here we are reporting insights into insecticidal activity of a plant natural phenol. In silico and in vitro screening of multiple molecules supported by in vivo validations suggested that caffeic acid (CA) is a potent inhibitor of Helicoverpa armigera gut proteases. Protease activity and gene expression were altered in CA-fed larvae. The structure–activity relationship of CA highlighted that all the functional groups are crucial for inhibition of protease activity. Biophysical studies and molecular dynamic simulations revealed that sequential binding of multiple CA molecules induces conformational changes in the protease(s) and thus lead to a significant decline in their activity. CA treatment significantly inhibits the insect’s detoxification enzymes, thus intensifying the insecticidal effect. Our findings suggest that CA can be implicated as a potent insecticidal molecule and explored for the development of effective dietary pesticides.