Inhibition of hepatic S-3-hydroxy-3-methylglutaryl-CoA reductase and in vivo rates of lipogenesis by a mixture of pure cyclic monoterpenes

Abstract

A proprietary mixture of pure cyclic monoterpenes (Rowachol) inhibited hepatic HMGCoA reductase by 50–60% when measured 17 hr after the oral administration of a single dose to rats. The extent of this inhibition was independent of the normal activity range of HMGCoA reductase within its diurnal cycle and the same inhibition (65%) was found in 24 hr starved animals where the control reductase activity was less than 20% that of normal fed rats. De novo sterol and fatty acid synthesis in intact, fed rats was measured by incorporation of 3H from injected H 2O. In rats treated with Rowachol the rate of sterol synthesis in vivo was inhibited 52% in liver and 44% in testis with no significant effects in other tissues. The synthesis of non sterol (isoprenoid) compounds in testis was unaffected and the inhibition of sterol synthesis in this tissue probably reflects decreased acquisition of newly synthesized material from liver rather than any effect on the endogenous process. In the same animals the rate of fatty acid synthesis was inhibited 55% in liver. These effects were associated with a significant depletion of liver glycogen which may account for the reduction in rate of fatty acid synthesis. We conclude that the reported cholelitholytic action of monoterpenes is associated with the physiological inhibition of hepatic sterol synthesis mediated by decreased HMGCoA reductase activity.