Cyclooxygenase‐2 Expression and Prostaglandin E2 production in Chondrocytes are Inhibited by the Combination of Avocado Soy Unsaponifiables (ASU) and Epigallocatechin gallate (EGCG)

Abstract

Production of the pro-inflammatory mediator prostaglandin E2 (PGE2) is catalyzed by the cyclooxygenase-2 (COX-2) enzyme. Suppression of PGE-2 and COX-2 expression by non-steroidal anti-inflammatory drugs reduces pain and but causes gastrointestinal (GI) complications. Recently, ASU and EGCG from green tea extracts have been evaluated independently for providing relief in chronic inflammatory disorders. We hypothesize that the combination of ASU and EGCG inhibits COX-2 expression and PGE2 synthesis. Chondrocytes (5×105cells/well) from bovine and equine cartilage were incubated for 24 hrs with: control media alone, ASU (8.3 μg/ml NMX1000™-ASU), EGCG (0.4 μg/ml), or with the combination of ASU and EGCG. Cells were then activated with lipopolysaccharide (20 ng/ml) or IL-1β (10 ng/ml) for 1 or 24 hrs. Pre-treatment with the combination of ASU and EGCG profoundly suppressed COX-2 expression in activated chondrocytes by as much as 60%. This reduction was associated with decreased PGE2 production. The inhibitory effect of the combination was more pronounced than either agent alone. Our study demonstrates the combination of ASU and EGCG down-regulates the COX-2 gene that controls PGE2 synthesis. This combination may offer an alternative approach to reduce inflammation while minimizing adverse GI effects. Research supported by Nutramax Laboratories, Inc. and Mississippi State University.