title: Hepato-protective effects of loganin, iridoid glycoside from Corni Fructus, against hyperglycemia-activated signaling pathway in liver of type 2 diabetic db/db mice.
abstract: Accumulating evidence indicates that uncontrolled diabetes leads to the progression of diabetic complications such as liver disorder. The present study was carried out to elucidate the protective role of loganin extracted from Corni Fructus against hepatic oxidative stress caused by type 2 diabetes. Loganin (20 or 100mg/kg body weight/day, p.o.) was administered every day for 8 weeks to db/db mice, and its effect was assessed on comparison with vehicle-treated db/db and m/m mice. The administration of loganin led to a decrease in glucose and elevation of leptin in serum. The diabetic oxidative stress was attenuated by loganin through inhibitions of reactive oxygen species production and lipid peroxidation in the serum and liver. The expression of proteins induced by oxidative stress was significantly up-regulated in the liver of diabetic db/db mice; however, the expressions of both Nox-4 and p22(phox) were decreased significantly by loganin administration. Loganin showed a crucial effect in the inflammation-activated signaling pathway through the regulation of NF-κB, COX-2, and iNOS. It was also found to regulate the anti-inflammatory factors Nrf-2 and HO-1 in hepatic tissue. Moreover, expression of MCP-1 was significantly down-regulated in the loganin-treated db/db mice. Furthermore, loganin administration showed a protective effect against apoptosis by the regulation of Bcl-2 and cytochrome c. The present study demonstrated that the administration of loganin isolated from Corni Fructus had a protective effect against hepatic oxidative stress under type 2 diabetes through regulations of protein expressions related to oxidative stress, inflammation, and apoptosis.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Chan Hum
authors.initials: CH
authors.lastname: Park
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Cho
authors.forename: Jong Cheol
authors.initials: JC
authors.lastname: Park
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Shibahara
authors.forename: Takako
authors.initials: T
authors.lastname: Yokozawa
mesh_terms: D000818:Animals; D029768:Cornus; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control*; D006943:Hyperglycemia / Q000378:metabolism / Q000517:prevention & control*; D057889:Iridoid Glycosides / Q000494:pharmacology / Q000627:therapeutic use; D039823:Iridoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D057889:Iridoid Glycosides; D039823:Iridoids; D020011:Protective Agents; D017382:Reactive Oxygen Species; C059516:loganin