Impact of a Withania somnifera and Bacopa monnieri Formulation on SH-SY5Y Human Neuroblastoma Cells Metabolism Through NMR Metabolomic

<b>Objectives</b>: This study investigates the effectiveness of an herbal formulation, STRESSLESS (ST-65), which combines ashwagandha (<i>Withania somnifera</i>) and bacopa (<i>Bacopa monnieri</i>), on SH-SY5Y human neuroblastoma cells. Given the rising interest in natural compounds for neuroprotection and stress alleviation, we aimed to explore the cellular and molecular effects of this formulation. <b>Methods</b>: Utilizing a nuclear magnetic resonance (NMR) metabolomic approach and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS), we identified key bioactive compounds in ST-65, including withanolides from ashwagandha and bacosides from bacopa. <b>Results</b>: Our findings indicate that ST-65 treatment significantly alters the metabolic profile of SH-SY5Y cells. Key changes included increased levels of metabolites linked to neuroprotection, energy metabolism, and antioxidant defense. Notable enhancements were observed in specific amino acids and neuroprotective compounds, suggesting activation of neuroprotective mechanisms and mitigation of stress-induced damage. <b>Conclusions</b>: The study reveals a complex phyto-chemical profile of ST-65 and underscores its potential as a natural active agent for addressing stress-related neurodegenerative conditions. These insights into neuronal mechanisms provide a foundation for further exploration of herbal formulations in neuroprotection.