标准化越橘提取物对改善情绪低落和增强认知能力的机制研究及潜在健康益处。

mechanistic studies and potential health benefits of a standardized bilberry extract in low mood and cognitive enhancement.

作者信息

Kara Mehtap, Hasbal-Celikok Gozde, Wilson Jacob, Gómez-Serranillos Pilar, Yilmaz-Ozden Tugba, Öztas Ezgi, Özhan Gul, Zengin Özge Sultan, Gómez-Serranillos Marta Sánchez, Owsianik Claudia, Rabbani Fazle, Tunç Merve, Arda Nazlı, Memon Nazia M, Ujjan Ikram, Hawkins Kenny, Davis Justine, Wilson Gabriel, Petrangolini Giovanna, Khan Amjad

机构信息

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Türkiye.

Department of Biochemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Türkiye.

出版信息

Front Nutr. 2025 Jul 31;12:1630147. doi: 10.3389/fnut.2025.1630147. eCollection 2025.

Abstract

BACKGROUND

Low mood and cognitive impairments are multifactorial conditions often linked to oxidative stress, neurotransmitter imbalances, and neuroinflammation. Bilberry () 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

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 GABA 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 HO, 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 ( = 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 GABA receptor binding. It exhibited robust antioxidant activity in DPPH (EC: 9.24 ± 0.22 μg/mL), ABTS (EC: 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 ( < 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.

摘要

背景

情绪低落和认知障碍是多因素导致的状况,常与氧化应激、神经递质失衡及神经炎症相关。越橘提取物富含花青素,近期研究显示其具有良好的神经药理学特性。

研究目的

本研究旨在全面评估标准化越橘提取物(Mirtoselect™)的生化、抗氧化及神经保护特性,并在临床环境中评估其对情绪和认知提升的潜在健康益处。

方法

进行实验以探究越橘提取物的神经调节、抗氧化及细胞保护特性。酶抑制实验针对γ-氨基丁酸转氨酶(GABA-T)、单胺氧化酶A(MAO-A)和乙酰胆碱酯酶(AChE),同时也评估GABA受体结合情况。使用DPPH、ABTS、FRAP、ORAC、HORAC和TAS实验评估抗氧化能力。利用暴露于过氧化氢的SH-SY5Y细胞研究神经保护作用,评估细胞活力(MTT)、膜完整性(LDH释放)和脑源性神经营养因子(BDNF)表达。通过SH-SY5Y细胞的MTT实验确定细胞毒性。对健康成年受试者(n = 33)(年龄25 - 55岁)进行一项随机、双盲、安慰剂对照的初步临床研究,以评估越橘提取物对情绪(POMS)和认知功能的影响。

结果

越橘提取物对GABA-T、MAO-A和AChE有显著抑制作用,同时对GABA受体有适度结合。在DPPH(EC₅₀:9.24 ± 0.22 μg/mL)、ABTS(EC₅₀:12.70 ± 0.11 μg/mL)、FRAP、ORAC、HORAC和TAS实验中表现出强大的抗氧化活性。神经保护作用包括在氧化应激下增强SH-SY5Y细胞的活力、减少LDH释放以及上调BDNF。细胞毒性测试证实其安全性良好。在初步研究中,与安慰剂相比,补充越橘提取物显著改善了情绪参数,包括降低紧张、抑郁和困惑得分(P < 0.05),且不良反应最小。

结论

越橘提取物具有强大的抗氧化、神经调节和神经保护特性,支持其作为改善情绪低落和认知健康的天然干预措施的潜力。良好的安全性和初步临床益处值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57c/12352346/dc0c672ddc0b/fnut-12-1630147-g001.jpg

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