ABSTRACT
Introduction .................................................................................................................................... 474 Pycnogenol® ................................................................................................................................... 474 Pathophysiogy of OA ..................................................................................................................... 474
Role of In–ammation ............................................................................................................ 474 In–ammatory Mediators ....................................................................................................... 475 Cytokines and Growth Factors.............................................................................................. 475 Matrix Metalloproteinases .................................................................................................... 476 Nitric Oxide .......................................................................................................................... 477 C-Reactive Protein ................................................................................................................ 477 Other Risk Factors and Biomarkers in OA ........................................................................... 477
Biological Pro—le of Pycnogenol ................................................................................................... 477 Antioxidant and Anti-in–ammatory Activities ..................................................................... 477 Antioxidant Effects: In Vitro Studies .................................................................................... 478 Antioxidant and Anti-in–ammatory Activities: In Vivo Animal Studies ............................... 479 Antioxidant Effects: Clinical Studies ................................................................................... 479 Inhibition of MMPs .............................................................................................................. 479 Inhibition of Cytokines .........................................................................................................480
Clinical Research in OA ................................................................................................................480 Ef—cacy Data .........................................................................................................................480
Mechanisms of Action ................................................................................................................... 482 Lowering of CRP, Free Radicals, and Fibrinogen Levels in Plasma .................................... 482 Ex Vivo Studies in Healthy Human Volunteers ..................................................................... 483
