Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D-2 levels

Dried roots of the plants Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis are used in traditional oriental medicine and reportedly possess anti-inflammatory properties. Using the murine air pouch model of inflammation, we investigated the efficacy and mode of action of an extract from these three plants in crystal-induced inflammation. Air pouches were raised on the backs of 8-week-old BALB/c mice. Mice were fed 100 mg/kg body weight of root extracts ( A. senticosus: A. sinensis: S. baicalensis mixed in a ratio of 5: 4: 1 by weight) or vehicle only on days 3-6. Inflammation was elicited on day 6 by injecting 2 mg of monosodium urate ( MSU) crystals into the pouch. Neutrophil density and IL- 6 and TNF-alpha mRNA levels were determined in the pouch membrane, and the leukocyte count and IL- 6, prostaglandin E-2 ( PGE(2)) and prostaglandin D-2 ( PGD(2)) levels were determined in the pouch exudate. Treatment with the root extracts led to a reduction in all inflammatory parameters: the leukocyte count in the pouch exudate decreased by 82%; the neutrophil density in the pouch membrane decreased by 68%; IL- 6 and TNF-alpha mRNA levels in the pouch membrane decreased by 100%; the IL- 6 concentration in the pouch fluid decreased by 50%; and the PGE(2) concentration in the pouch fluid decreased by 69%. Remarkably, the concentration of the potentially anti-inflammatory PGD(2) rose 5.2-fold in the pouch exudate ( p < 0.005), which led to a normalization of the PGD(2): PGE(2) ratio. A 3.7-fold rise in hematopoietic PGD synthase (h-PGDS) mRNA paralleled this rise in PGD(2) (p=0.01). Thus, the root extracts diminished MSU crystal-induced inflammation by reducing neutrophil recruitment and expression of pro-inflammatory factors and increasing the level of the potentially anti-inflammatory PGD(2). These results support a need for further studies of the efficacy of these extracts in the treatment of inflammatory arthropathies and suggest elevation of PGD(2) levels as a novel mechanism for an anti-inflammatory agent.