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Inhibitors of hyaluronan export from hops prevent osteoarthritic reactions
Author(s) -
Stracke Dennis,
Schulz Tobias,
Prehm Peter
Publication year - 2011
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201000210
Subject(s) - chemistry , xanthohumol , phosphodiesterase , proteoglycan , pharmacology , biochemistry , osteoarthritis , hyaluronic acid , aggrecan , overproduction , cartilage , multidrug resistance associated proteins , atp binding cassette transporter , enzyme , transporter , hop (telecommunications) , medicine , extracellular matrix , articular cartilage , anatomy , computer network , alternative medicine , pathology , computer science , gene
Scope: An early reaction in osteoarthritic chondrocytes is hyaluronan overproduction followed by proteoglycan loss and collagen degradation. We recently found that hyaluronan is exported by the ATP‐binding cassette transporter multidrug resistance associated protein 5 (MRP5) in competition with cGMP and that some phosphodiesterase 5 inhibitors also inhibited hyaluronan export. These inhibitors also prevented osteoarthritic reactions in cartilage. In an effort to identify the improved inhibitors directed primarily toward MRP5, we analyzed the flavonoids Methods and results: Prenylflavonoids from hop xanthohumol, isoxanthohumol and 8‐prenylnaringenin inhibited MRP5 export at lower concentrations than phosphodiesterase 5 activity. They were analyzed for their effect on IL‐induced osteoarthritic reactions in bovine chondrocytes. Xanthohumol was the superior compound to inhibit hyaluronan export, as well as proteoglycan and collagen loss. It also prevented the shedding of metalloproteases into the culture medium. It directly inhibited MRP5, because it reduced the export of the MRP5 substrate fluorescein immediately and did not influence the hyaluronan synthase activity. Conclusions: Xanthohumol may be a natural compound to prevent hyaluronan overproduction and subsequent reactions in osteoarthritis.