Osteoarthritis (OA) is characterized by inflammation, joint immobility, and pain. Non-pharmacologic agents modulating pro-inflammatory mediator expression offer considerable promise as safe and effective treatments for OA. We previously determined the anti-inflammatory effect of an avocado/soybean unsaponifiables (ASU) and epigallocatechin gallate (EGCG) combination on prostaglandin E2 (PGE2) production and nuclear factor-kappa B (NF-κB) translocation. The aim of this study was to evaluate the effects of ASU + EGCG on pro-inflammatory gene expression.

Objective: Pro-inflammatory mediators such as prostaglandin E-2 (PGE₂) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE₂ can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design: Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) control media, (2) ASU, (3) LA, or (4) ASU + LA combination. Cells were activated with lipopolysaccharide (LPS), interleukin 1β (IL-1β) or hydrogen peroxide (H₂O₂) for 24 hours and supernatants were immunoassayed for PGE₂. Nuclear factor-kappa B (NF-κB) analyses were performed by immunocytochemistry and Western blot following 1 hour of activation with IL-1β. Results: LPS, IL-1β, or H₂O₂ significantly increased PGE₂ production. ASU or LA alone suppressed PGE₂ production in LPS and IL-1β activated cells. Only LA alone at 2.5 µg/mL was inhibitory in H₂O₂-activated chondrocytes. ASU + LA inhibited more than either agent alone in all activated cells. ASU + LA also inhibited the IL-1β induced nuclear translocation of NF-κB. Conclusions: The present study provides evidence that chondrocyte PGE₂ production can be inhibited by the combination of ASU + LA more effectively than either ASU or LA alone. Inhibition of PGE₂ production is associated with the suppression of NF-κB translocation. The potent inhibitory effect of ASU + LA on PGE₂ production could offer a potential advantage for a combination anti-inflammatory/antioxidant approach in the management of OA.

Tendinopathy, a common disorder in man and horses, is characterized by pain, dysfunction, and tendon degeneration. Inflammation plays a key role in the pathogenesis of tendinopathy. Tendon cells produce proinflammatory molecules that induce pain and tissue deterioration. Currently used nonsteroidal anti-inflammatory drugs are palliative but have been associated with adverse side effects prompting the search for safe, alternative compounds. This study determined whether tendon-derived cells' expression of proinflammatory cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE ₂ ) could be attenuated by the combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS). ASU, GLU, and CS have been used in the management of osteoarthritis-associated joint inflammation. Tenocytes in monolayer and microcarrier spinner cultures were incubated with media alone, or with the combination of ASU (8.3 μ g/mL), GLU (11 μ g/mL), and CS (20 μ g/mL). Cultures were next incubated with media alone, or stimulated with interleukin-1 β (IL-1 β ; 10 ng/mL) for 1 h to measure COX-2 gene expression, or for 24 h to measure PGE ₂ production, respectively. Tenocyte phenotype was analyzed by phase-contrast microscopy, immunocytochemistry, and Western blotting. Tendon-derived cells proliferated and produced extracellular matrix component type I collagen in monolayer and microcarrier spinner cultures. IL-1 β -induced COX-2 gene expression and PGE ₂ production were significantly reduced by the combination of (ASU+GLU+CS). The suppression of IL-1 β -induced inflammatory response suggests that (ASU+GLU+CS) may help attenuate deleterious inflammation in tendons.