Luteolin stimulates the NGF-induced neurite outgrowth in cultured PC12 cells. - GreenMedInfo Summary
Luteolin stimulates the NGF-induced neurite outgrowth in cultured PC12 cells through binding with NGF and potentiating its receptor signaling.
Food Funct. 2021 Nov 15 ;12(22):11515-11525. Epub 2021 Nov 15. PMID: 34704574
Alex Xiong Gao
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% (<0.01), as well as the increased expression of neurofilaments by 119± 32.1% (<0.05), 191± 12.6% (<0.01), and 110± 23.4% (<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.