RT Journal Article T1 In vitro mechanistic studies and potential health benefits of a standardized bilberry extract in low mood and cognitive enhancement A1 Kara, Methap A1 Hasbal-Celikok, Gozde A1 Wilson, Jacob A1 Gómez-Serranillos Cuadrado, María Pilar A1 Yilmaz-Ozden, Tugba A1 Öztas, Ezgi A1 Özhan, Gul A1 Zengin, Özge Sultan A1 Sánchez Gómez-Serranillos, Marta A1 Owsianik, Claudia A1 Rabbani, Fazle A1 Tunç, Merve A1 Arda, Nazli A1 Memon, Nazia M. A1 Ujjan, Ikram A1 Hawkins, Kenny A1 Davis, Justine A1 Wilson, Gabriel A1 Petrangolini, Giovanna A1 Khan, Amjad AB Background: Low mood and cognitive impairments are multifactorial conditions often linked to oxidative stress, neurotransmitter imbalances, and neuroinflammation. Bilberry (Vaccinium myrtillus L.) extract, particularly rich in anthocyanins, has shown promising neuropharmacological properties in recent studies.Aims of the study: This study aimed to comprehensively evaluate the biochemical, antioxidant, and neuroprotective properties of a standardized bilberry extract (Mirtoselect™), alongside assessing its potential health benefits on mood and cognitive enhancement in a clinical setting.Methods: In vitro assays were conducted to explore the neuromodulatory, antioxidant, and cytoprotective properties of Bilberry extract. Enzyme inhibition assays targeted γ-Aminobutyric acid transaminase (GABA-T), monoamine oxidase A (MAO-A), and acetylcholinesterase (AChE), while GABAA receptor binding was also evaluated. Antioxidant capacity was assessed using DPPH, ABTS, FRAP, ORAC, HORAC, and TAS assays. Neuroprotection was investigated using SH-SY5Y cells exposed to H2O2, assessing cell viability (MTT), membrane integrity (LDH release), and BDNF expression. Cytotoxicity was determined through the MTT assay in SH-SY5Y cells. A randomized, double-blind, placebo-controlled pilot clinical study was conducted on healthy adult subjects (n = 33) (aged 25–55 years) to evaluate the effects of Bilberry extract on mood (POMS) and cognitive function.Results: Bilberry extract demonstrated significant inhibition of GABA-T, MAO-A, and AChE, alongside moderate GABAA receptor binding. It exhibited robust antioxidant activity in DPPH (EC50: 9.24 ± 0.22 μg/mL), ABTS (EC50: 12.70 ± 0.11 μg/mL), FRAP, ORAC, HORAC, and TAS assays. Neuroprotective effects included enhanced cell viability, reduced LDH release, and upregulation of BDNF in SH-SY5Y cells under oxidative stress. Cytotoxicity tests confirmed a favorable safety profile. In the pilot study, Bilberry extract supplementation significantly improved mood parameters, including reduced tension, depression, and confusion scores (p < 0.05) compared to placebo, with minimal adverse effects.Conclusion: Bilberry extract exhibits potent antioxidant, neuromodulatory, and neuroprotective properties, supporting its potential as a natural intervention for managing low mood and cognitive health. The favorable safety profile and preliminary clinical benefits warrant further research. PB Frontiers Media YR 2025 FD 2025-07-31 LK https://hdl.handle.net/20.500.14352/125047 UL https://hdl.handle.net/20.500.14352/125047 LA eng NO Kara M, Hasbal-Celikok G, Wilson J, Gómez-Serranillos P, Yilmaz-Ozden T, Öztas E, Özhan G, Zengin ÖS, Gómez-Serranillos MS, Owsianik C, Rabbani F, Tunç M, Arda N, Memon NM, Ujjan I, Hawkins K, Davis J, Wilson G, Petrangolini G, Khan A. In vitro mechanistic studies and potential health benefits of a standardized bilberry extract in low mood and cognitive enhancement. Front Nutr 2025;12:1630147. https://doi.org/10.3389/fnut.2025.1630147. DS Docta Complutense RD 18 oct 2025