Inhibitors of hyaluronan export from hops prevent osteoarthritic reactions.

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Stracke D, Schulz T, Prehm P

Inhibitors of hyaluronan export from hops prevent osteoarthritic reactions.

Mol Nutr Food Res. 2011 Mar;55(3):485-94. doi: 10.1002/mnfr.201000210. Epub 2010 Sep 16.

PubMed ID

20848398 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Hyaluronic acid	Multidrug resistance-associated protein 5	Protein	Humans	Unknown	Substrate	Details