Identification and quantification of kukoamine A and kukoamine B as novel μ-opioid receptor agonists in potato and other solanaceous plants

Abstract

Activation of the µ-opioid receptor (µOR) by food components could lead to reward effects or to the modulation of motor functions in the gastrointestinal tract. In an unbiased search for novel µOR agonists in food, a three-step virtual-screening process selected 22 promising candidates with potential to interact with the µOR. Radioligand binding studies showed that ten of these substances indeed bind to the receptor. Functional assays identified kukoamine A as a full agonist (EC₅₀ = 5.6 µM) and kukoamine B as a partial agonist (EC₅₀ = 8.7 µM) to µOR. After extraction, both kukoamines were analyzed by LC-MS/MS in potato, tomato, pepper, and eggplant. Depending on the potato variety, up to 16 µg of kukoamine A and 157 µg of kukoamine B per gram dry weight could be determined in the whole tuber, mainly concentrated in the potato peel. Cooking did not influence the kukoamine contents.

Keywords: Bioactive food compound; Kukoamine; Potato; Solanaceous plant; Virtual screening; µ-Opioid receptor.