Evaluation of loganin, iridoid glycoside from Corni Fructus, on hepatic and renal glucolipotoxicity and inflammation in type 2 diabetic db/db mice.
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.
Yamabe
Noriko
N
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Noh
Jeong Sook
JS
Park
Chan Hum
CH
Kang
Ki Sung
KS
Shibahara
Naotoshi
N
Tanaka
Takashi
T
Yokozawa
Takako
T
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D029768:Cornus / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004326:Drinking / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006403:Hematologic Tests; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D039823:Iridoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
C466220:(6)-2-methoxy-6-heptadecenoic acid; D015415:Biomarkers; D005227:Fatty Acids; D017127:Glycation End Products, Advanced; D039823:Iridoids; D047493:PPAR alpha; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D051996:Transcription Factor RelA; D014280:Triglycerides; C048496:N(6)-carboxymethyllysine; D002784:Cholesterol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C059516:loganin; D005947:Glucose; D008239:Lysine