Evaluation of loganin, iridoid glycoside from Corni Fructus, on hepatic and renal glucolipotoxicity and inflammation in type 2 diabetic db/db mice

Abstract

Previously, we have reported that Corni Fructus possessed hypoglycemic and hypocholesterolemic effects in streptozotocin-induced type 1 diabetic rats and diet-induced hypercholesterolemic rats. Herein, we have focused on the effect and mechanism of loganin, a major iridoid glycoside of Corni Fructus, on the type 2 diabetic db/db mice. Loganin was orally administered to db/db mice at a dose of 20 or 100 mg/kg body weight daily for 8 weeks. The biochemical factors and expressions of protein and mRNA related to lipid metabolism, inflammation, advanced glycation endproducts, and its receptor were measured. In loganin-treated db/db mice, hyperglycemia and dyslipidemia were ameliorated in both the serum and hepatic tissue; however, in the kidney, only triglyceride was reduced. The enhanced oxidative stress was alleviated by loganin through a decrease in thiobarbituric acid-reactive substances (liver and kidney) and reactive oxygen species (serum, liver, and kidney), as well as augmentation of the oxidized to reduced glutathione ratio (liver and kidney). The marked lipid-regulatory effect of loganin was exerted in the liver of type 2 diabetic mice via suppressing mRNA expressions related to lipid synthesis and adjusting the abnormal expression of peroxisome proliferator-activated receptor α and sterol regulatory-element binding protein in the nucleus. Furthermore, loganin inhibited advanced glycation endproduct formation and the expression of its receptor, and nuclear factor-kappa B-induced inflammation in the hepatic tissue of db/db mice. Loganin exhibits protective effects against hepatic injury and other diabetic complications associated with abnormal metabolic states and inflammation caused by oxidative stress and advanced glycation endproduct formation.