ArticlePloS one2011
Neurotrophic effect of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone: promotion of neurite outgrowth via cAMP/PKA/CREB pathway in PC12 cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- The cellular model for Alzheimer's disease research: PC12 cells.Frontiers in molecular neuroscience · 2022Pooled it
- Effects of Peripheral Nerve Injury on the Induction of c-Fos and Phosphorylated ERK in the Brainstem Trigeminal Sensory Nuclear Complex.Annals of neurosciences · 2023Article
- Sudachitin and Nobiletin Stimulate Lipolysis via Activation of the cAMP/PKA/HSL Pathway in 3T3-L1 Adipocytes.Foods (Basel, Switzerland) · 2023Article
- Article
- Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders.Nutrients · 2021Review
- Nimodipine promotes neurite outgrowth and protects against neurotoxicity in PC12 cells.Iranian journal of basic medical sciences · 2021Article
- Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral squamous cell carcinoma.Food science & nutrition · 2020Article
- The Bu Shen Yi Sui Formula Promotes Axonal RegenerationFrontiers in pharmacology · 2019Article
- Toxic effect of acrylamide on the development of hippocampal neurons of weaning rats.Neural regeneration research · 2017Article
- Modulation of neurotrophic signaling pathways by polyphenols.Drug design, development and therapy · 2016Review
- PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling.Cell death and differentiation · 2015Article
- Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism.PloS one · 2015Article
- Rapamycin promotes Schwann cell migration and nerve growth factor secretion.Neural regeneration research · 2014Article
- Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary neurons and human SH-SY5Y neuroblastoma cells.International journal of molecular sciences · 2013Article
- Capsaicin-induced activation of ERK1/2 and its involvement in GAP-43 expression and CGRP depletion in organotypically cultured DRG neurons.Cellular and molecular neurobiology · 2013Article
- Role of oxidative stress in refractory epilepsy: evidence in patients and experimental models.International journal of molecular sciences · 2013Review
- Nobiletin Ameliorates the Deficits in Hippocampal BDNF, TrkB, and Synapsin I Induced by Chronic Unpredictable Mild Stress.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Neurotrophic effect of citrus auraptene: neuritogenic activity in PC12 cells.International journal of molecular sciences · 2012Article
- Article
- Luteolin induces microRNA-132 expression and modulates neurite outgrowth in PC12 cells.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF), a hydroxylated polymethoxyflavone, is found exclusively in the Citrus genus, particularly in the peels of sweet orange. In this research, we report the first investigation of the neurotrophic effects and mechanism of 5-OH-HxMF in PC12 pheochromocytoma cells. We found that 5-OH-HxMF can effectively induce PC12 neurite outgrowth accompanied with the expression of neuronal differentiation marker protein growth-associated protein-43(GAP-43). 5-OH-HxMF caused the enhancement of cyclic AMP response element binding protein (CREB) phosphorylation, c-fos gene expression and CRE-mediated transcription, which was inhibited by 2-naphthol AS-E phosphate (KG-501), a specific antagonist for the CREB-CBP complex formation. Moreover, 5-OH-HxMF-induced both CRE transcription activity and neurite outgrowth were inhibited by adenylate cyclase and protein kinase A (PKA) inhibitor, but not MEK1/2, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K) or calcium/calmodulin-dependent protein kinase (CaMK) inhibitor. Consistently, 5-OH-HxMF treatment increased the intracellular cAMP level and downstream component, PKA activity. We also found that addition of K252a, a TrKA antagonist, significantly inhibited NGF- but not 5-OH-HxMF-induced neurite outgrowth. These results reveal for the first time that 5-OH-HxMF is an effective neurotrophic agent and its effect is mainly through a cAMP/PKA-dependent, but TrKA-independent, signaling pathway coupling with CRE-mediated gene transcription. A PKC-dependent and CREB-independent pathway was also involved in its neurotrophic action.
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