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Biol Pharm Bull. 2017;40(10):1724-1729. doi: 10.1248/bpb.b17-00324.

Echinocystic Acid Facilitates Neurite Outgrowth in Neuroblastoma Neuro2a Cells and Enhances Spatial Memory in Aged Mice.

Author information

1
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University.
2
Department of Aquatic Biomedical Sciences, School of Marine Biomedical Science, College of Ocean Science, Jeju National University.
3
Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University.
4
Department of Life and Nanopharmaceutical Science, Kyung Hee University.
5
Institute of Convergence Bio-health, Dong-A University.

Abstract

Aging leads to functional changes in the brain and decreases ability of learning and memory. Neurite outgrowth is important in learning and memory, therefore regulation of neurite outgrowth might be a candidate for treating aged brain. Echinocystic acid (EA), a pentacyclic triterpene, has shown to exert various neurological effects. However, the effect of EA on neurite outgrowth has not been studied. In this study, we examined if EA is effective on neurite outgrowth and memory in aged mice. The effect of EA on neurite outgrowth was observed by examining neurite processes of Neuro2a cells treated with EA. Western blot analysis was conducted to examine possible mechanisms. Morris water maze test was used to examine the effect of EA on learning and memory in aged mice. Immunohistochemistry was conducted to observe the effect of EA on neurite outgrowth in the hippocampus. EA was shown to induce neurite outgrowth in a concentration dependent manner without affecting cell viability. Moreover, EA treatment increased phosphorylation of c-jun N-terminal kinase (JNK) and JNK inhibitor, SP600125, blocked the effect of EA on neurite outgrowth. These results demonstrated that EA treatment promotes neurite outgrowth through the JNK signaling pathway. In in vivo experiments, EA treatment increased neurite outgrowth in aged mouse hippocampus. Moreover, EA treatment enhanced spatial learning and memory in aged mice. These results suggest that EA can be developed as a new, naturally occurring drug to treat ageing-related neurological diseases.

KEYWORDS:

aging; echinocystic acid; neurite outgrowth; spatial memory

PMID:
28966244
DOI:
10.1248/bpb.b17-00324
[Indexed for MEDLINE]
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