xanthohumol and Osteoarthritis

Osteoarthritis (OA), manifested as degeneration and damage of the articular cartilage is a progressive disease of joints. Previous studies have shown that extracellular matrix degradation and inflammation have quite a significant performance in the occurrence and development of OA. In various maladies, an anti-inflammatory effect has been demonstrated for Xanthohumol (XN); while OA is an inflammation related disease. The current in vivo and in vitro study aimed to investigate the therapeutic effect of XN on OA as well as its working mechanism. The results showed that XN has the capability to hinder the expression of nitric oxide synthase (INOS), IL-1β-promoted inducible nitric oxide (NO), necrosis factor-α of tumor (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in vitro. In addition, XN has been found to down-regulate the expression of matrix metalloproteinase-13 and prothrombin stimulated by IL-1β and up-regulates type II collagen and Aggrecan expression. At the same time, it was discovered that XN activates nuclear factor (Nrf2) in chondrocytes stimulated by IL-1β and inhibits nuclear factor B (NF-кB) signal transduction. The DMM model manifests that XN has an inhibitory impact on the progression of osteoarthritis and thus may be a candidate drug to slow down and delay the development of OA.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Chondrocytes; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Flavonoids; Inflammation Mediators; Joints; Male; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Propiophenones; Signal Transduction

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.

Topics: Animals; ATP-Binding Cassette Transporters; Cattle; Cells, Cultured; Chondrocytes; Collagen; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Flavanones; Flavonoids; Humulus; Hyaluronic Acid; Multidrug Resistance-Associated Proteins; Osteoarthritis; Phosphodiesterase 5 Inhibitors; Plant Extracts; Propiophenones; Proteoglycans; Xanthones