Premium
Identification of Human‐Flavonoid Targets Using an Innovative Approach Reveals New Mechanisms Involved in Their Anti‐Inflammatory Activities
Author(s) -
Arango Daniel,
Morohashi Kengo,
Yilmaz Alper,
Brahimaj Bledi,
Kuramochi Kouji,
Grotewold Erich,
Doseff Andrea I.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.251.5
Subject(s) - apigenin , nutraceutical , computational biology , inflammation , biology , flavonoid , microbiology and biotechnology , biochemistry , immunology , antioxidant
Flavonoids are dietary nutraceuticals with anti‐carcinogenic, chemopreventive, and anti‐inflammatory activities. We showed that apigenin, a flavone broadly found in fruits and vegetables, has anti‐inflammatory activity in vitro and in a mouse model of inflammation through the regulation of NF‐κB. However, its molecular mechanisms of action remain unknown. The goal of this study was to identify the human cellular targets of apigenin. We developed and implemented a novel approach coupling phage‐display with next‐generation sequencing (PD‐Seq) to identify human cellular targets of apigenin. Targets were validated using competition and pull down assays, with purified GST and GFP‐tagged proteins and cellular lysates. Development of a FRET‐nanosensor using a newly identified target provided insightful structure‐binding relationships of flavonoids. Molecular cell‐based studies showed that the apigenin target plays central roles in inflammation and reveals novel aspects on how nutraceuticals regulate immunity. Altogether, these results suggest that the innovative use of phage display in combination with next‐generation sequencing provides a robust method to identify novel targets of flavonoids. The findings reveal novel aspects on how nutraceuticals regulate biological activities providing better insights for the rational development of functional foods. Grant Funding Source : This work was supported by Grants RO1HL075040‐01 and NSF‐MCB‐0542244 to AID and by OSUPHPID fellowship to DA