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Article: Botanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK1/2 and PI3K/Akt Signaling Pathways in the Neurite Extension Process

TitleBotanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK1/2 and PI3K/Akt Signaling Pathways in the Neurite Extension Process
Authors
Issue Date2015
Citation
CNS Neuroscience & Therapeutics, 2015, v. 21 n. 1, p. 61-70 How to Cite?
AbstractAim: Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular-signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. The present study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process. Methods: We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP-lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2 and HO-1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit. Results: Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP-lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold. Mechanistic studies revealed: 1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase-1 (HO-1) pathways; 2) ERK1/2, PI3K/Akt and HO-1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF-induced neuritogenesis in a timing-dependent manner. Conclusion: Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases.
Persistent Identifierhttp://hdl.handle.net/10722/206103

 

DC FieldValueLanguage
dc.contributor.authorZhao, Jen_US
dc.contributor.authorCheng, Yen_US
dc.contributor.authorFan, Wen_US
dc.contributor.authorYang, Cen_US
dc.contributor.authorYe, Sen_US
dc.contributor.authorCui, Wen_US
dc.contributor.authorWei, Wen_US
dc.contributor.authorLao, Len_US
dc.contributor.authorCai, Jen_US
dc.contributor.authorHan, YFen_US
dc.contributor.authorRong, Jen_US
dc.date.accessioned2014-10-20T12:20:06Z-
dc.date.available2014-10-20T12:20:06Z-
dc.date.issued2015-
dc.identifier.citationCNS Neuroscience & Therapeutics, 2015, v. 21 n. 1, p. 61-70en_US
dc.identifier.urihttp://hdl.handle.net/10722/206103-
dc.description.abstractAim: Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular-signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. The present study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process. Methods: We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP-lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2 and HO-1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit. Results: Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP-lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold. Mechanistic studies revealed: 1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase-1 (HO-1) pathways; 2) ERK1/2, PI3K/Akt and HO-1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF-induced neuritogenesis in a timing-dependent manner. Conclusion: Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases.en_US
dc.languageengen_US
dc.relation.ispartofCNS Neuroscience & Therapeuticsen_US
dc.titleBotanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK1/2 and PI3K/Akt Signaling Pathways in the Neurite Extension Processen_US
dc.typeArticleen_US
dc.identifier.emailLao, L: lxlao1@hku.hken_US
dc.identifier.emailRong, J: jrong@hku.hken_US
dc.identifier.authorityLao, L=rp01784en_US
dc.identifier.authorityRong, J=rp00515en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/cns.12334-
dc.identifier.hkuros241244en_US

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