title: JAK2 and AMP-kinase inhibition in vitro by food extracts, fractions and purified phytochemicals.
abstract: We have identified a range of food phytochemicals that inhibit Janus Kinase 2 (JAK2) and Adenosine Monophosphate Kinase (AMPK). A mutated and dysregulated form of JAK2, a tyrosine kinase, is associated with several diseases including Crohn's disease. Using an in vitro, time-resolved fluorescence (TR-FRET) assay, we tested 49 different types of food extracts, plus 10 concentrated fractions of increasing hydrophobicity from each extract, to find foods containing JAK2 inhibitors. The food extracts tested included grains, meat, fish, shellfish, dairy products, herbs, mushrooms, hops, fruits and vegetables. Several fruits were potent inhibitors of JAK2: blackberry, boysenberry, feijoa, pomegranate, rosehip and strawberry, which all contain ellagitannins, known inhibitors of kinases. These fruits are in the Rosales and Myrtales plant orders. No other foods gave >1% of the maximal JAK2 inhibitory activities of these fruits. AMPK, a sensor and regulator of energy metabolism in cells, is a serine-threonine kinase which is reported to be activated by various flavonoid phytochemicals. Using a TR-FRET assay, we tested various fruit extracts for AMPK activation and inhibition. Ellagitannin containing foods scored highly as AMPK inhibitors. Despite several reports of AMPK activation in whole cells by phytochemicals, no extracts or pure compounds activated AMPK in our assay.
authors.affiliation: Food Innovation, The New Zealand Institute for Plant & Food Research Ltd, Private Bag 11 600, Palmerston North 4442, New Zealand. harry.martin@plantandfood.co.nz.
authors.forename: Harry
authors.initials: H
authors.lastname: Martin
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Burgess
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Smith
authors.forename: Tony K
authors.initials: TK
authors.lastname: McGhie
authors.forename: Janine M
authors.initials: JM
authors.lastname: Cooney
authors.forename: Rona C M
authors.initials: RC
authors.lastname: Lunken
authors.forename: Erika
authors.initials: E
authors.lastname: de Guzman
authors.forename: Tania
authors.initials: T
authors.lastname: Trower
authors.forename: Nigel B
authors.initials: NB
authors.lastname: Perry
mesh_terms: D029042:Actinidia / Q000737:chemistry; D000263:Adenylate Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D003424:Crohn Disease / Q000178:diet therapy / Q000201:enzymology / Q000235:genetics; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D005504:Food Analysis; D005638:Fruit / Q000737:chemistry*; D055951:Functional Food; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry; D009154:Mutation; D009520:New Zealand; D064209:Phytochemicals / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D019685:Rosales / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D007527:Isoenzymes; D064209:Phytochemicals; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; C013515:ellagitannin; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D000263:Adenylate Kinase