Xanthohumol for treating diseases associated with hyaluronan overproduction
Hyaluronan is the major water binding component of the extracellular matrix. It is exported into the extracellular matrix by fibroblasts, where it attracts water up to 99 % of its own weight, swells to enormous volumes and displaces other resident macromolecules. Elevated hyaluronan synthesis leads to disturbances of cell behaviour, tissue integrity and hydration.
Hyaluronan overproduction is found in pathological disturbances such as metastasis, inflammation, oedema and osteoarthritis. There is an ongoing need to provide inhibitors which are able to reduce the hyaluronan export.
We discovered that hyaluronan is exported from fibroblasts and chondrocytes by MRP5. We also showed that unspecific inhibitors of MRP5 export prevented migration and metastasis of melanoma cells. These inhibitors also prevented hyaluronan overproduction, proteoglycan loss and collagen degradation in osteoarthritic cartilage and in an animal model of osteoarthritis. Since these inhibitors were not specific, we search for natural compounds and identified xanthohumol from hops that inhibited hyaluronan export specifically.
A European patent application has been filed.
Advantages of the invention
The following diseases may be treated with the xanthohumol:
ischemic or inflammatory oedema: metastatic tumours which are characterized by an overproduction of hyaluronan such as melanoma, mesothelioma or colon carcinoma, lump formation after contusion or insect bites, injuries/conditions which are followed by inflammation and hyaluronan overproduction like heart infarct, alveolitis, pancreatitis, pulmonary or hepatic fibrosis, radiation induced inflammation, Crohn´s disease, myocarditis, scleroderma, psoriasis, sarcoidosis. Xanthohumol could not only be administered therapeutically, but also prophylactically.
New aspects of the invention
Natural products from hops have been used non-specifically for well-being, but no therapeutic targets were known. Here we propose xanthohumol as a drug for diseases that are accompanied by hyaluronan overproduction.