Z-Guggulsterone Improves the Scopolamine-Induced Memory Impairments Through Enhancement of the BDNF Signal in C57BL/6J Mice.
Memory impairment is a common symptom in patients with neurodegenerative disorders, and its suppression could be beneficial to improve the quality of life of those patients. Z-guggulsterone, a compound extracted from the resin of plant Commiphora whighitii, exhibits numerous pharmacological effects in clinical practice, such as treatment of inflammation, arthritis, obesity and lipid metabolism disorders. However, the role and possible mechanism of Z-guggulsterone on brain-associated memory impairments are largely unknown. This issue was addressed in the present study in a memory impairment model induced by scopolamine, a muscarinic acetylcholine receptor antagonist, using the passive avoidance, Y-maze and Morris water maze tests. Results showed that scopolamine significantly decreased the step-through latency and spontaneous alternation of C57BL/6J mice in passive avoidance and Y-maze test, whereas increased the mean escape latency and decreased the swimming time in target quadrant in Morris water maze test. Pretreatment of mice with Z-guggulsterone at doses of 30 and 60 mg/kg effectively reversed the scopolamine-induced memory impairments. Mechanistic studies revealed that Z-guggulsterone pretreatment reversed the scopolamine-induced increase in acetylcholinesterase (AchE) activity, as well as decreases in brain-derived neurotrophic factor (BDNF) protein expression and cAMP response element-binding protein (CREB), extracellular regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) phosphorylation levels in the hippocampus and cortex. Inhibition of the BDNF signal, however, blocked the memory-enhancing effect of Z-guggulsterone. Therefore, these findings demonstrate that Z-guggulsterone attenuates the scopolamine-induced memory impairments mainly through activation of the CREB-BDNF signaling pathway, thereby exhibiting memory-improving effects.
Invasive Technology Department, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, #6 North Road Hai'er Xiang, Nantong, 226001, Jiangsu, China.
Zhuo
Z
Chen
Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong, 226001, Jiangsu, China. huachao@ntu.edu.cn.
Chao
C
Huang
Invasive Technology Department, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, #6 North Road Hai'er Xiang, Nantong, 226001, Jiangsu, China. ntjrdr@126.com.
Wenbin
W
Ding
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation; D011282:Pregnenediones / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012601:Scopolamine; D015398:Signal Transduction
D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018697:Nootropic Agents; D011282:Pregnenediones; C023617:pregna-4,17-diene-3,16-dione; D012601:Scopolamine; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000110:Acetylcholinesterase
BDNF; CREB; Memory impairment; Scopolamine; Z-guggulsterone
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