Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption

The authors are grateful to B. Fellah, I. Leborgne, and P. Roy (CRIP-ONIRIS) who contributed to experiments using rabbits; S. Sourice (Inserm UMRS 791) for her advice with histological analysis; E. Hay (Inserm UMRS 1132) for his advice with NITEGE IHC; P.Pilet for his fruitful discussion for IHC intensity analysis; F. Berenbaum for his help in DMM mice model; UTE Platform (SFR Francois Bonamy, FED 4203/ Inserm UMS 016/CNRS 3556) who provided daily care to animals and specially P. Monmousseau who provided help with forced-fed rabbits; MS and NMR experiments were undertaken at the Metabolome Facility at the Functional Genomic Center in Bordeaux, France and specially E. Renouf for her assistance in UPLC-MS analysis. R Pace who provided help with manuscript. This study was supported by Grap'Sud, Region Languedoc Roussillon, the BPI and the ANRTInternational audiencePolyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration. Anti-inflammatory and chondroprotective actions of HT/PCy were tested on primary cultured rabbit chondrocytes stimulated by interleukin-1 beta (IL-1β). The results showed that HT/PCy exerts anti-inflammatory and chondroprotective actions in vitro. The preventive effect of HT/PCy association was assessed in two animal models of post-traumatic OA in mice and rabbits. Diet supplementation with HT/PCy significantly decreased the severity of post-traumatic osteoarthritis in two complementary mice and rabbit models. The bioavailability and bioactivity was evaluated following gavage with HT/PCy in rabbits. Regular metabolites from HT/PCy extract were found in sera from rabbits following oral intake. Finally, sera from rabbits force-fed with HT/PCy conserved anti-IL-1β effect, suggesting the bioactivity of this extract. To conclude, HT/PCy extract may be of clinical significance for the preventive treatment of osteoarthritis