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5,6,7,4′‐Tetramethoxyflavanone alleviates neurodegeneration in a dexamethasone‐induced neurodegenerative mouse model through promotion of neurogenesis via the Raf/ ERK1 /2 pathway
Author(s) -
Pakdeepak Kanet,
Chokchaisiri Ratchanaporn,
Govitrapong Piyarat,
Tocharus Chainarong,
Suksamrarn Apichart,
Tocharus Jiraporn
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6983
Subject(s) - neurogenesis , doublecortin , neural stem cell , biology , microbiology and biotechnology , neuroscience , stem cell , dentate gyrus , hippocampal formation
Adult neurogenesis plays an important role in improving cognitive functions. Neurogenesis generates new neurons, a process mediated by neural stem cell proliferation, migration, and differentiation. Long‐term exposure to high levels of glucocorticoid results in the suppression of neurogenesis pathways and leads to the onset of cognitive impairment. The induction of neurogenesis by a potent bioactive compound is considered the most promising treatment for neurodegenerative disorders. 5,6,7,4′‐Tetramethoxyflavanone (TMF) is a flavonoid compound isolated from Chromolaena odorata (L.) R. M. King & H. Rob. Previous study showed that TMF improved cognitive impairment by attenuating Aβ production and pTau expression, thereby increased cell survival and promoted synaptic plasticity. The aim of this study was to investigate the effect of TMF on dexamethasone (DEX)‐suppressed neurogenesis in mice. Mice received DEX for 28 days before being treated with TMF for additional 30 days. Mice were randomly divided into four groups: control, TMF, DEX, and DEX + TMF. TMF promoted neurogenesis by increasing BrdU‐positive cells, Prox1, doublecortin, and Nestin expression. TMF also upregulated the expression of Raf and extracellular‐signal‐regulated kinase (ERK)1/2, which are pivotal for neurogenesis signaling. In conclusion, TMF promoted neurogenesis‐related protein expression in the proliferation, differentiation, and maturation phases via Raf/ERK1/2 signaling pathway.