The effect of morroniside on lipid metabolism and the inflammatory response in the liver of type 2 diabetes model mice was investigated in this study. Male C57BLKS/J db/db mice were divided into the three groups: control (vehicle), morroniside 20, or 100 mg/kg body weight-treated mice. The elevated serum triglyceride and alanine aminotransferase levels as well as hepatic glucose and lipids contents in db/db mice were significantly decreased by the 8-week oral administration of morroniside in a dose-dependent manner. The generations of hepatic thiobarbituric acid-reactive substances and reactive oxygen species induced by hyperglycemia and dyslipidemia were also significantly decreased by the administration of morroniside. In addition, the barometer of an antioxidative state, the oxidized to reduced glutathione ratio, in the liver of db/db mice was markedly increased by morroniside treatment. From protein analysis, the elevated expressions of nuclear factor-κBp65, cyclooxygenase-2, inducible nitric oxide synthase, and sterol regulatory element binding proteins (SREBP-1 and SREBP-2) were down-regulated in the liver of db/db mice. On the other hand, the administration of morroniside significantly increased hepatic peroxisome proliferator activated receptor α expression. These results suggest that morroniside would act as a regulator of hepatic inflammatory reactions and lipid metabolism in db/db mice.
2009 The Pharmaceutical Society of Japan