Anti-amnesic effect of Dendropanax morbifera via JNK signaling pathway on cognitive dysfunction in high-fat diet-induced diabetic mice.
The ameliorating effects of the ethyl acetate fraction from Dendropanax morbifera (EFDM) on cognitive impairment in high-fat diet (HFD)-induced diabetic mice were examined by measuring its possible pharmacological activities. Administration of EFDM (20 and 50mg/kg body weight) in HFD-induced diabetic mice significantly improved glucose tolerance status in the intraperitoneal glucose tolerance test (IPGTT). In animal experiments using Y-maze, passive avoidance and Morris water maze tests, the cognitive and behavioral disorders in HFD-induced diabetic mice were considerably recovered by regulating cholinergic systems, including acetylcholine (ACh) levels and acetylcholinesterase (AChE) inhibition, and antioxidant systems, including superoxide dismutase (SOD), glutathione (GSH), oxidized GSH, and malondialdehyde (MDA) levels. Furthermore, HFD-induced abnormal activity of mitochondria were also significantly protected by the improvement of the c-Jun N-terminal protein kinase (JNK) signaling pathway with phosphorylated JNK (p-JNK), phosphorylated insulin receptor substrate (p-IRS), serine/threonine protein kinase (Akt), phosphorylated Akt (p-Akt), and phosphorylated tau (p-tau). Finally, rutin, orientin, isoorientin, and luteolin-7-O-rutinoside as the main phenolics of EFDM were identified using ultra-performance liquid chromatography/quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS(2)). These findings suggest that EFDM may have an effect as a multiple preventive substances to reduce diabetes-associated cognitive dysfunction.
Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, South Korea.
Jong Min
JM
Kim
Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, South Korea.
Seon Kyeong
SK
Park
Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, South Korea.
Tian Jiao
TJ
Guo
Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, South Korea.
Jin Yong
JY
Kang
Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, South Korea.
Jeong Su
JS
Ha
Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, South Korea.
Du Sang
du S
Lee
Division of Special Purpose Tree, National Institute of Forest Science, Suwon 16631, South Korea.
Uk
U
Lee
Division of Applied Life Science (BK21 plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, South Korea. Electronic address: hjher@gnu.ac.kr.
Ho Jin
HJ
Heo
D000085:Acetates / Q000008:administration & dosage* / Q000302:isolation & purification; D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D019803:Glutathione Disulfide / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019684:Magnoliopsida; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000378:metabolism
D000085:Acetates; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010936:Plant Extracts; C007650:ethyl acetate; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D000109:Acetylcholine; D019803:Glutathione Disulfide
Cognitive impairment; Dendropanax morbifera; Diabetes mellitus; JNK pathway; Luteolin; Rutin