Effect of benzylidene derivative (novel antirheumatic agent) on chondrocyte metabolism.

The effects of protocatechualdehyde (PAL), one of the metabolites of 3,4-diacetoxy benzylidene diacetate (ACP), on proteoglycan metabolism and secretion of interleukin 1 (IL-1) like activity (lymphocyte activating factor; LAF activity) were studied using rabbit articular chondrocytes culture under phorbol myristate acetate (PMA) and Ca2+ ionophore A23187 (A23187) or IL-1 alpha stimulation. In IL-1 alpha (20 u/ml) or PMA (0.1 micrograms/ml) and A23187 (0.2 micrograms/ml) treated culture of rabbit articular chondrocytes, PAL significantly reduced the degradation of 35S-proteoglycan (35S-PG) from the cells and matrix layers into the culture media in a dose dependent fashion without affecting proteoglycan synthesis. Similarly, the secretion or production of matrix metalloproteinases which degrade proteoglycans was also inhibited to the same extent under IL-1 alpha stimulated condition. However, PAL caused no effect on the secretion of IL-1 like activity by chondrocytes. These results suggest that an attractive candidate for an anti-inflammatory drug, ACP, which is a prodrug of PAL, has also a favorable action on chondrocyte metabolism in terms of proteoglycan degradation via inhibition of matrix metalloproteinases secretion or production.