Bioactive constituents of Corni Fructus: The therapeutic use of morroniside, loganin, and 7-O-galloyl-D-sedoheptulose as renoprotective agents in type 2 diabetes.

Corni Fructus, the fruit of Cornus officinalis Sieb. et Zucc. (Cornaceae), is an important crude herb used in Chinese medicine to exhibit several biological activities, including hypoglycemic, antineoplastic, and antimicrobial effects, and to improve liver and kidney functions. We have been investigating the mechanism and bioactive constituents of Corni Fructus using diabetic animal models. Morroniside, loganin, and 7-O-galloyl-D-sedoheptulose, the main active compounds of Corni Fructus, exhibit the same lowering effects of elevated triglyceride, oxidative stress and advanced glycation endproduct (AGE) formation in the kidney of db/db mice. The effects of morroniside and 7-O-galloyl-D-sedoheptulose were mediated through modulation by renal sterol regulatory element binding proteins and nuclear factor-kappa B expression, but the effect of loganin was presumably mediated by hypoglycemic and antioxidant effects in the kidney, and also indirectly by the amelioration of metabolic disorders in other organs such as the liver. These findings led us to conclude that morroniside, loganin, and 7-O-galloyl-D-sedoheptulose would synergistically contribute to the inhibition of metabolic disorders (hyperglycemia and dyslipidemia), oxidative stress, inflammation, as well as AGE formation in the diabetic kidney.