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Z-Guggulsterone Improves the Scopolamine-Induced Memory Impairments Through Enhancement of the BDNF Signal in C57BL/6J Mice

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Abstract

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.

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Abbreviations

AchE:

Acetylcholinesterase

AD:

Alzheimer’s disease

BDNF:

Brain-derived neurotrophic factor

CREB:

cAMP response element-binding protein

DMSO:

Dimethylsulfoxide

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Acknowledgments

This work was supported by the Natural Science Foundation of China (No. 81571323), the Natural Science Foundation of Jiangsu Province (No. BK20141240) and the Science and Technology Project of Nantong City (No. MS12015050) to Dr Chao Huang.

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Authors and Affiliations

  1. 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 Chen & Wenbin Ding

  2. Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong, 226001, Jiangsu, China

    Chao Huang

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  1. Zhuo Chen
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Correspondence to Chao Huang or Wenbin Ding.

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Chen, Z., Huang, C. & Ding, W. Z-Guggulsterone Improves the Scopolamine-Induced Memory Impairments Through Enhancement of the BDNF Signal in C57BL/6J Mice. Neurochem Res 41, 3322–3332 (2016). https://doi.org/10.1007/s11064-016-2064-0

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