Evaluation of Proliferative Activity of Hawaiian Plants on PC-12 and Neuro-2a Cells and Their Effect on the TPH and TH Genes

<b>Background/Objectives</b>: Neurotransmitters such as dopamine and serotonin are critical regulators of mood, cognition, and neuronal homeostasis. This study aimed to evaluate the neuropharmacological potential of Hawaiian plants by investigating their ability to modulate the expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), key enzymes in neurotransmitter biosynthesis. <b>Methods</b>: A total of 108 aqueous and methanolic extracts of Hawaiian plants were screened for cytotoxicity against PC-12 and Neuro-2A cells using the MTT assay. Fifty-six non-toxic extracts were selected and further analyzed for TH and TPH expression via quantitative real-time PCR (qPCR). <b>Results</b>: Several extracts significantly upregulated TH and TPH expression without inducing cytotoxicity. Extracts derived from <i>Morinda citrifolia</i>, <i>Pipturus albidus</i>, and <i>Hedychium coronarium</i> showed the most notable activity, suggesting their potential to enhance dopaminergic and serotonergic pathways. <b>Conclusions</b>: The findings highlight the promise of native Hawaiian flora as sources of neuroactive compounds that may support neuroprotection and regeneration. These results provide a foundation for in vivo studies and further exploration of novel neurotherapeutic agents.