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.

• Authors: Noriko Yamabe, Jeong Sook Noh, Chan Hum Park, Ki Sung Kang, Naotoshi Shibahara, Takashi Tanaka, Takako Yokozawa
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 648 Issue 1-3 Pg. 179-87 (Dec 01 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20826139 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• (6)-2-methoxy-6-heptadecenoic acid
• Biomarkers
• Fatty Acids
• Glycation End Products, Advanced
• Iridoids
• PPAR alpha
• RNA, Messenger
• Sterol Regulatory Element Binding Protein 1
• Sterol Regulatory Element Binding Protein 2
• Transcription Factor RelA
• Triglycerides
• N(6)-carboxymethyllysine
• Cholesterol
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• loganin
• Glucose
• Lysine

Topics

• Animals
• Biomarkers (metabolism)
• Body Weight (drug effects)
• Cholesterol (metabolism)
• Cornus (chemistry)
• Cyclooxygenase 2 (metabolism)
• Diabetes Mellitus, Type 2 (complications, drug therapy, metabolism, pathology)
• Drinking (drug effects)
• Fatty Acids (metabolism)
• Gene Expression Regulation, Enzymologic (drug effects)
• Glucose (metabolism)
• Glycation End Products, Advanced (metabolism)
• Hematologic Tests
• Inflammation (complications, drug therapy)
• Iridoids (isolation & purification, pharmacology, therapeutic use)
• Kidney (drug effects, metabolism, pathology)
• Lipid Metabolism (drug effects, genetics)
• Liver (drug effects, metabolism, pathology)
• Lysine (analogs & derivatives, metabolism)
• Male
• Mice
• Nitric Oxide Synthase Type II (metabolism)
• Organ Size (drug effects)
• Oxidative Stress (drug effects)
• PPAR alpha (metabolism)
• RNA, Messenger (genetics, metabolism)
• Sterol Regulatory Element Binding Protein 1 (metabolism)
• Sterol Regulatory Element Binding Protein 2 (metabolism)
• Transcription Factor RelA (metabolism)
• Triglycerides (metabolism)