PMID- 27677871 OWN - NLM STAT- MEDLINE DCOM- 20170315 LR - 20181202 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 41 IP - 12 DP - 2016 Dec TI - Z-Guggulsterone Improves the Scopolamine-Induced Memory Impairments Through Enhancement of the BDNF Signal in C57BL/6J Mice. PG - 3322-3332 AB - 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. FAU - Chen, Zhuo AU - Chen Z AD - 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. FAU - Huang, Chao AU - Huang C AD - Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong, 226001, Jiangsu, China. huachao@ntu.edu.cn. FAU - Ding, Wenbin AU - Ding W AD - 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. LA - eng PT - Journal Article DEP - 20160928 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Nootropic Agents) RN - 0 (Pregnenediones) RN - A4PW148END (pregna-4,17-diene-3,16-dione) RN - DL48G20X8X (Scopolamine) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.1.1.7 (Acetylcholinesterase) SB - IM MH - Acetylcholinesterase/metabolism MH - Animals MH - Avoidance Learning/drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cerebral Cortex/drug effects/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Hippocampus/drug effects/metabolism MH - Male MH - Maze Learning/drug effects MH - Memory Disorders/chemically induced/*drug therapy/metabolism MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Nootropic Agents/*pharmacology/therapeutic use MH - Phosphorylation MH - Pregnenediones/*pharmacology/therapeutic use MH - Proto-Oncogene Proteins c-akt/metabolism MH - Scopolamine MH - Signal Transduction OTO - NOTNLM OT - BDNF OT - CREB OT - Memory impairment OT - Scopolamine OT - Z-guggulsterone EDAT- 2016/09/30 06:00 MHDA- 2017/03/16 06:00 CRDT- 2016/09/29 06:00 PHST- 2016/05/20 00:00 [received] PHST- 2016/09/15 00:00 [accepted] PHST- 2016/09/07 00:00 [revised] PHST- 2016/09/30 06:00 [pubmed] PHST- 2017/03/16 06:00 [medline] PHST- 2016/09/29 06:00 [entrez] AID - 10.1007/s11064-016-2064-0 [pii] AID - 10.1007/s11064-016-2064-0 [doi] PST - ppublish SO - Neurochem Res. 2016 Dec;41(12):3322-3332. doi: 10.1007/s11064-016-2064-0. Epub 2016 Sep 28.