Inhibitors of hyaluronan export from hops prevent osteoarthritic reactions.
Summary of "Inhibitors of hyaluronan export from hops prevent osteoarthritic reactions."
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 flavonoidsMethods 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.
Muenster University Hospital, Institute of Physiological Chemistry and Pathobiochemistry, Muenster, Germany.
This article was published in the following journal.
Name: Molecular nutrition & food research
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20848398
- DOI: http://dx.doi.org/10.1002/mnfr.201000210
Medical and Biotech [MESH] Definitions
Nuclear Export Signals
Specific amino acid sequences present in the primary amino acid sequence of proteins which mediate their export from the CELL NUCLEUS. They are rich in hydrophobic residues, such as LEUCINE and ISOLEUCINE.
Neurotransmitter Uptake Inhibitors
Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.
An alcoholic beverage usually made from malted cereal grain (as barley), flavored with hops, and brewed by slow fermentation.
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