The capacity of the human brain to enable growth of neurons occurs through neural stem cell differentiation guided by trophic factors such as brain‐derived neurotrophic factor or nerve growth factor (NGF). Elevated levels of NGF are believed to play a protective role in preventing a diverse range of age related neurodegenerative conditions. Moreover, PC‐12 dopaminergic cells are a valuable model for evaluating neuroprotective / trophic agents relevant to Parkinson's disease. In this study, we screened 1145 compounds [29 flavonoids, 168 synthetic drugs, 948 herb, fruit and vegetable extracts] for NGF mimetic effects in PC‐12 cells in the absence of NGF. The data indicate that 2 natural products of the 1145 tested at sub‐lethal concentrations had capacity to initiate neurite outgrowth comparable to NGF, which acquired properties of sympathetic neurons. Differentiation was analyzed by fluorescent immunocytochemistry Alexa (488)‐conjugated phalloidin / propidium iodide nuclear counterstain and contrast microscopy in live cells. These data support very unique properties of few natural products to mimic the effects of NGF.Grant Funding Source: Supported by NIMHD G12 MD007582 and P20 MD006738