RESTORATIVE EFFECT OF SHOSAIKOTO (KAMPO MEDICINE) ON DIMINUTION OF NITRIC-OXIDE SYNTHESIS IN MURINE PERITONEAL-MACROPHAGES INDUCED BY HYPERCHOLESTEROLEMIA

Macrophages play important roles both in immune response and in lipid metabolism and contribute to the development of atherosclerosis. To cl arify the mechanism by which Shosaikoto, a Kampo medicine, shows anti- atherosclerotic action, we studied its effect on macrophage function. The production of nitric oxide (NO), prostaglandin E(2) and interleuki n 1 by macrophages in mice was reduced by feeding of a cholesterol-enr iched diet, and the reduced production was observed 1 week after the b eginning of cholesterol feeding. Furthermore, although oxidized low de nsity lipoprotein (LDL) and lysophosphatidylcholine (LPC) reduced NO p roduction, macrophages prepared from mice treated with Shosaikoto at a dose of 1.2g/kg/d restored the reduced NO production by them as well as by hypercholesterolemia. When the content of LPC was measured, no d ifference was observed between mice fed a cholesterol-enriched diet in the presence of absence of Shosaikoto treatment, suggesting that the restorative effect of Shosaikoto is not due to the inhibition of LPC p roduction or accumulation. Conclusively, Shosaikoto prevents the modif ication of macrophage function induced by atherogenic factors, which i s probably linked to its displayed anti-atherosclerotic action.