Muenster University Hospital, Institute of Physiological Chemistry and Pathobiochemistry, Muenster, Germany.
Mol Nutr Food Res. 2011 Mar;55(3):485-94. doi: 10.1002/mnfr.201000210. Epub 2010 Sep 16.
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.
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.
Xanthohumol may be a natural compound to prevent hyaluronan overproduction and subsequent reactions in osteoarthritis.
骨关节炎软骨细胞的早期反应是透明质酸过度产生，随后是蛋白聚糖丢失和胶原降解。我们最近发现，透明质酸通过 ATP 结合盒转运蛋白多药耐药相关蛋白 5（MRP5）与 cGMP 竞争被输出，一些磷酸二酯酶 5 抑制剂也抑制了透明质酸的输出。这些抑制剂也防止了软骨中的骨关节炎反应。为了寻找主要针对 MRP5 的改良抑制剂，我们分析了类黄酮。
来自啤酒花的黄腐酚、异黄腐酚和 8-异戊烯基柚皮素等 prenylflavonoids 以低于磷酸二酯酶 5 活性的浓度抑制 MRP5 输出。它们被分析用于抑制 IL 诱导的牛软骨细胞中的骨关节炎反应。黄腐酚是抑制透明质酸输出以及蛋白聚糖和胶原丢失的优越化合物。它还防止了金属蛋白酶脱落到培养基中。它直接抑制 MRP5，因为它立即减少了 MRP5 底物荧光素的输出，并且不影响透明质酸合酶活性。
黄腐酚可能是一种天然化合物，可以预防透明质酸过度产生和随后的骨关节炎反应。
