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Plant-derived modulators of inflammation and cartilage metabolism

By S. Hougee

Abstract

Currently the treatment of chronic inflammatory diseases is aimed at inhibiting the symptoms of the disease since there are no curative or preventive treatments available. Rheumatoid arthritis (RA) is a painful chronic inflammatory disease of the joints. Osteoarthritis (OA) is a disease in which pain and inflammation of the joint in certain (end-) stages of the disease plays an important role. For variable reasons patients use natural products to relieve their symptoms, with many claims that have insufficient scientific evidence unfortunately. In this thesis a selection of phytochemicals and plant extracts was investigated for their potential modulating effects on inflammatory processes and on chondrocyte cartilage metabolism relevant for OA and RA. Most of these are suitable for nutritional purposes. Different test systems were used, ranging from in vitro experiments with both animal and human cells, to in vivo animal experiments. A bioavailability study in human healthy volunteers was performed as well. Among the tested flavonoids, apigenin, chrysin and luteolin eliminated monocytes/macrophages from white blood cells in vitro, whereas quercetin and naringenin had no effects. An extract of Pterocarpus marsupium demonstrated inhibitory activity of prostaglandin E2 (PGE2) which was related to the pterostilbene content of the extract. Moreover, from whole blood assays it became clear that it reduced PGE2 produced by cyclooxygenase (COX)-2 and not by COX-1. In a pilot study with human healthy volunteers the extract was not active. An extract of hop (Humulus lupulus) showed to inhibit PGE2 produced by COX-2 and not by COX-1. In an animal study for acute arthritis oral administration of the hop extract did not result in reduced joint swelling although it was bioavailable. Oral administration of apocynin was able to confirm two in vitro observed features in vivo: (1) oral administration of apocynin was able to reverse zymosan-induced inhibition of cartilage proteoglycan synthesis partially, and (2) oral administration of apocynin showed COX inhibitory effects similar to the NSAID ibuprofen. SKI306X, a preparation of a mix of three oriental plants (Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris), has been studied in OA patients. The in vitro studies described in this thesis demonstrated that the biological effects of SKI306X are at least bipartite: (1) cartilage protective and (2) anti-inflammatory. In conclusion, the results from this thesis illustrate that there is a large potential of plant-derived components as anti-inflammatory agents. However, further research, which includes clinical trials in the relevant patient groups, has to elucidate whether these plant-derived components are appropriate candidates as anti-inflammatory agents suitable for nutritional purposes

Topics: Farmacie, Flavonoids, Pterocarpus marsupium, pterostilbene, Humulus lupulus, apocynin, SKI306X, anti-inflammatory, cartilage metabolism, PGE2, cyclooxygenase
Publisher: Utrecht University
Year: 2008
OAI identifier: oai:dspace.library.uu.nl:1874/26187
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