Anti-inflammatory and cartilage protective effects of punicalagin, a major hydrolyzable tannin isolated from pomegranate, and a crude red raspberry extract in vitro and in vivo
Rheumatoid Arthritis (RA) is the most common form of inflammatory condition that is characterized by a chronic inflammation that leads to the irreversible destruction of cartilage and functional disability. Cartilage degradation in RA results from the degradation of its two main protein components, type II collagen (CII) and proteoglycans. Despite recent therapeutic advances, there is an urgent need for strategies that will work to reduce the excess mortality consistently associated with this disease. Many polyphenols have been shown to possess anti-inflammatory properties in vitro and in vivo. The Primary focus of this thesis was to evaluate the effects of punicalagin (PA), a polyphenol isolated from pomegranate, and a crude red raspberry on cartilage degradation and inflammation in RA. In the first manuscript, the inhibitory effects of PA on MMP-13 activity were investigated in vitro using type II collaen as a substrate and its effects were compared with other well-selected polyphenols that include epigallocatechin gallate, quercetin and curcumin. MMP-13 is a major enzyme involved in the degradation of cartilage. Punicalagin was found to inhibit MMP-13 activity in a dose-dependent manner and was more potent than epigallocatechin gallate, quercetin and curcumin. Our preliminary data suggested that PA can bind both MMP-13 and CII and that the inhibition by PA might involve direct interactions with MMP-13. Binding interactions of PA and with CII were investigated using molecular docking simulations and Surface Plasmon Resonance. The data revealed tight interaction of PA to CII. PA was then tested in an explants model of cartilage degradation and an experimental model of antigen-induced arthritis in rats. The data shows that PA holds great potential against the inflammatory and destructive pathways in RA. The second manuscript reports the cartilage protecting and anti-inflammatory effects of red raspberry in vitro and in vivo. This study has led to the conclusion that regular consumption of red raspberry may help reduce inflammation and maintain joint health.
"Anti-inflammatory and cartilage protective effects of punicalagin, a major hydrolyzable tannin isolated from pomegranate, and a crude red raspberry extract in vitro and in vivo"
Dissertations and Master's Theses (Campus Access).