Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microglia

Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E-2 (PGE(2) ) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE(2) synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 mum). In combination with acetylsalicylic acid (IC50 = 1.85 mum), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE(2) synthesis (IC50 = 0.25 mum in combination with 100 mum ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE(2) synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases.