Luteolin stimulates the NGF-induced neurite outgrowth in cultured PC12 cells through binding with NGF and potentiating its receptor signaling
| Autor: | Tina T. X. Dong, Tracy Chen-Xi Xia, Marvin Shing-Hung Mak, Karl Wah Keung Tsim, Kenneth Kin Leung Kwan, Brody Zhong-Yu Zheng, Alex Xiong Gao, Jian Xiao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Neurons
Neurite biology Cell Differentiation General Medicine Tropomyosin receptor kinase A CREB PC12 Cells Molecular biology Rats chemistry.chemical_compound Nerve growth factor nervous system chemistry Nerve Growth Factor Neurites biology.protein Animals K252a Luteolin Protein kinase B Signal Transduction Food Science Neurotrophin |
| Zdroj: | Food & Function. 12:11515-11525 |
| ISSN: | 2042-650X 2042-6496 |
| Popis: | Luteolin, a flavonoid in fruits and vegetables, has neurotrophic functions without a well-characterized mechanism. Here, we hypothesize a direct interaction of luteolin with nerve growth factor (NGF); as such, the functionality of the NGF could be potentiated. The direct binding of luteolin with NGF was validated by ultra-filtration, Biacore, and docking analyses. In cultured PC12 cells, application of luteolin in combination with a low dose of NGF potentiated the NGF-induced differentiation of neurons by an increase of the differentiated cell number to 25.4 ± 4.8% (p < 0.01), as well as the increased expression of neurofilaments by 119 ± 32.1% (p < 0.05), 191 ± 12.6% (p < 0.01), and 110 ± 23.4% (p < 0.05) for NF68, NF160 and NF200, respectively. The co-treatment induced the phosphorylations of tropomyosin receptor kinase A (TrkA), extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (Akt), phospholipase C-γ1 (PLCγ1), and cAMP response element-binding protein (CREB) by 2 to 3 fold: these induced phosphorylations were mimicking that of a high dose of NGF. Moreover, the application of the TrkA inhibitor, K252a, blocked the luteolin-mediated induction of neurofilament expression and neurite outgrowth in cultured PC12 cells, suggesting the target specificity. The result supports the development of luteolin as a therapeutic, or preventive, agent for NGF insufficiency-associated neurodegenerative diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|