Biological evaluation of nutraceuticals affecting cartilage metabolism and inflammation

Osteoarthritis is the most common joint disease and an important cause of physical disability. Clinical symptoms are frequently associated with a significant functional impairment and signs and symptoms of inflammation, including pain, stiffness and loss of mobility. In osteoarthritis the balance between cartilage synthesis and degradation is disturbed as a result of an altered mainly autocrine exposure of the chondrocytes to various cytokines and growth factors. RA is a chronic, inflammatory, systemic autoimmune disease. The cartilage and bone destruction in RA are directly linked to the exacerbation of inflammatory processes in the synovial membrane. The prevalence rates of osteoarthritis and rheumatoid arthritis are expected to increase in the coming years due to the increasing proportion of the elderly in the population. Up to 50% of the patients suffering from osteoarthritis or rheumatoid arthritis report the use of alternative remedies including natural products. These so-called nutraceuticals cover a broad range of products including nutrients, herbal preparations and dietary supplements. The way of action of a number of possible cartilage-protective and/or anti-inflammatory natural products is studied in vitro and in different in vivo mouse models A Grifola frondosa (Maitake) extract and a Centella asiatica fraction have been evaluated. Both, the Grifola frondosa extract and the Centella asiatica triterpenes fraction were able to stimulate glycosaminoglycan synthesis and inhibit proteoglycan degradation by bovine chondrocytes. In vivo studies demonstrated that the tested Centella asiatica fraction was able to inhibit the zymosan-induced cartilage degradation, although the zymosan-induced inflammatory cell infiltration and joint swelling were not affected. These results picture a cartilage protective effect. The herbal mixture SKI306X is on the market in Australia and Korea as a remedy for OA patients. The inhibitory effect of SKI306X and its individual herbal extracts on IL-1beta-induced proteoglycan degradation and nitric oxide and PGE2 production by bovine cartilage explants indicate a cartilage protective effect. Moreover, SKI306X also inhibits lipopolysaccharide-stimulated TNF-alpha, IL-1beta and PGE2 production by human peripheral blood mononuclear cells, demonstrating an anti-inflammatory and possibly an analgesic capacity. Apocynin can be isolated from the Himalayan herb Picrorhiza kurrooa. It was found that orally ingested apocynin partially counteracts the zymosan-induced inhibition of proteoglycan synthesis in the mouse knee joint. Moreover, apocynin is able to induce a cyclooxygenase inhibitory effect in mice, similar ibuprofen. The simple amino acid glycine and the milk protein lactoferrin have been indicated to contain anti-inflammatory and immune-modulatory activities. Both glycine and bovine lactoferrin are able to decrease ear swelling in a zymosan-induced ear-skin inflammation model. A combination of bovine lactoferrin and glycine counteracted the zymosan-induced ear swelling synergistically. The combination of glycine and bovine lactoferrin was tested in the collagen-induced arthritis mice model. Intervention with glycine and bovine lactoferrin results in a decrease in TNF-alpha and IL-6 cytokine serum levels and more importantly inhibition of arthritis development. The studied nutraceuticals are interesting candidates for the development of cartilage protective or anti-inflammatory agents for treatment of chronic inflammatory joint diseases such as osteoarthritis and rheumatoid arthritis