{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:41:30Z","timestamp":1781278890180,"version":"3.54.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Low mood and cognitive impairments are multifactorial conditions often linked to oxidative stress, neurotransmitter imbalances, and neuroinflammation. Bilberry (<jats:italic>Vaccinium myrtillus L.<\/jats:italic>) extract, particularly rich in anthocyanins, has shown promising neuropharmacological properties in recent studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims of the study<\/jats:title><jats:p>This study aimed to comprehensively evaluate the biochemical, antioxidant, and neuroprotective properties of a standardized bilberry extract (Mirtoselect\u2122), alongside assessing its potential health benefits on mood and cognitive enhancement in a clinical setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic> assays were conducted to explore the neuromodulatory, antioxidant, and cytoprotective properties of Bilberry extract. Enzyme inhibition assays targeted \u03b3-Aminobutyric acid transaminase (GABA-T), monoamine oxidase A (MAO-A), and acetylcholinesterase (AChE), while GABA<jats:sub><jats:italic>A<\/jats:italic><\/jats:sub> 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 H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, 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 (<jats:italic>n<\/jats:italic> = 33) (aged 25\u201355 years) to evaluate the effects of Bilberry extract on mood (POMS) and cognitive function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bilberry extract demonstrated significant inhibition of GABA-T, MAO-A, and AChE, alongside moderate GABA<jats:sub><jats:italic>A<\/jats:italic><\/jats:sub> receptor binding. It exhibited robust antioxidant activity in DPPH (EC<jats:sub>50<\/jats:sub>: 9.24 \u00b1 0.22 \u03bcg\/mL), ABTS (EC<jats:sub>50<\/jats:sub>: 12.70 \u00b1 0.11 \u03bcg\/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 (<jats:italic>p<\/jats:italic> &amp;lt; 0.05) compared to placebo, with minimal adverse effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1630147","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T15:45:59Z","timestamp":1753976759000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["In vitro mechanistic studies and potential health benefits of a standardized bilberry extract in low mood and cognitive enhancement"],"prefix":"10.3389","volume":"12","author":[{"given":"Mehtap","family":"Kara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gozde","family":"Hasbal-Celikok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"G\u00f3mez-Serranillos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tugba","family":"Yilmaz-Ozden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezgi","family":"\u00d6ztas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gul","family":"\u00d6zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zge Sultan","family":"Zengin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta S\u00e1nchez","family":"G\u00f3mez-Serranillos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Owsianik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazle","family":"Rabbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Tun\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazl\u0131","family":"Arda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia M.","family":"Memon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikram","family":"Ujjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Petrangolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/S2215-0366(23)00262-6","article-title":"Antidepressant and antipsychotic side-effects and personalised prescribing: A systematic review and digital tool development.","volume":"10","author":"Pillinger","year":"2023","journal-title":"Lancet Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"6021","DOI":"10.3390\/molecules27186021","article-title":"Medicinal plants used for anxiety, depression, or stress treatment: An update.","volume":"27","author":"Kenda","year":"2022","journal-title":"Molecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1934578X221139082","DOI":"10.1177\/1934578X221139","article-title":"Review of herbal medicines for the treatment of depression.","volume":"17","author":"Peng","year":"2022","journal-title":"Nat. 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