In Vitro Mechanistic Studies of a Standardized Sustainable Grape Seed Extract for Potential Application as a Mood-Modulating and Cognition-Enhancing Supplement – PubMed Black Hawk Supplements
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CONCLUSIONS: GSEe exhibits promising bioactivities, highlighting its potential as a supplement for modulating mood and enhancing cognitive function. Overall, the promising results from these in vitro studies provide a strong foundation for the continued exploration and development of GSEe as a viable natural supplement for enhancing mental health and cognitive function.
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. 2024 Oct 12;16(20):3459.
doi: 10.3390/nu16203459.
Gozde Hasbal-Celikok 1 , Mehtap Kara 2 , Marta Sánchez 3 , Claudia Owsianik 3 , Pilar Gómez-Serranillos 3 , Tugba Yilmaz-Ozden 1 , Ezgi Öztaş 2 , Özge Sultan Zengin 2 , Gul Ozhan 2 , Nazli Arda 4 , Merve Tunc 4 , Sumeyye Sahin 5 , Areaba Shafiq 6 , Ayesha Kanwal 6 , Hunaiba I Ujjan 7 , Fazle Rabbani 6 , Giovanna Petrangolini 8 , Amjad Khan 9 10
Affiliations
- PMID: 39458455
- PMCID: PMC11510545
- DOI: 10.3390/nu16203459
In Vitro Mechanistic Studies of a Standardized Sustainable Grape Seed Extract for Potential Application as a Mood-Modulating and Cognition-Enhancing Supplement
Gozde Hasbal-Celikok et al. Nutrients. .
Abstract
Background: Grape seed extract (GSE) from Vitis vinifera L. is rich in polyphenols and oligomeric proanthocyanidin complexes (OPCs), and it has shown potential benefits in managing low mood and cognitive function. In this study, we investigated the potential bioactivities of Enovita®, a standardized GSE extract (GSEe herein) rich in OPCs, in key mechanistic pathways related to low mood conditions and cognitive function.
Methods: In vitro assays were conducted to assess GSEe’s inhibitory effects on γ-aminobutyric acid transaminase (GABA-T) and monoamine oxidase A (MAO-A), its binding affinity to the GABA site of GABA-A receptors, and its effects on acetylcholinesterase (AChE). Its neuroprotective effects on human SH-SY5Y neuroblastoma cells under oxidative stress (induced by H2O2) were assessed using MTT and LDH release assays. Its antioxidant activities were evaluated using DPPH, ABTS, FRAP, ORAC, HORAC, total phenolic content, and TAS assays. Its cytotoxicity was also evaluated.
Results: GSEe showed significant GABA-T inhibitory activity. It also exhibited MAO-A and AChE inhibition, along with moderate binding affinity to the GABA-A receptor. In neuroprotective assays, GSEe provided significant protection to SH-SY5Y cells against oxidative stress. GSEe demonstrated robust antioxidant activity in all assays, including scavenging of DPPH and ABTS radicals, high ferric-reducing power, high polyphenolic contents, and a substantial total antioxidant capacity.
Conclusions: GSEe exhibits promising bioactivities, highlighting its potential as a supplement for modulating mood and enhancing cognitive function. Overall, the promising results from these in vitro studies provide a strong foundation for the continued exploration and development of GSEe as a viable natural supplement for enhancing mental health and cognitive function.
Keywords: Enovita®; GSEe; circular economy; cognitive function; grape seed extract; low mood; sustainability.
Conflict of interest statement
G.P. was an employee of Indena. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Figures

GABA-T inhibition assay of GSEe. The plot shows the percentage of GABA-T activity at various concentrations of GSEe, IC50 = 1.00 ± 0.20 mg/mL. A linear regression analysis was performed to determine the concentration-dependent inhibitory effect of GSEe on GABA-T activity. The error bars represent the standard deviation from the mean of the measurements of three freshly prepared samples.

Competitive binding of GSEe at the GABA site of rat GABA-A receptors, IC50 = 394.5 μg/mL. The error bars represent the standard deviation from the mean of the measurements of three freshly prepared samples.

MAO-A enzyme inhibition assay. The plot shows the effect of various concentrations of GSEe on the activity of the MAO-A enzyme. The error bars represent the standard deviation from the mean of the measurements of three freshly prepared samples.

AChE enzyme inhibition assay. The plot shows the effect of various concentrations of GSEe on the activity of the AChE enzyme, IC50 = 11.44 ± 0.83 µg/mL. The error bars represent the standard deviation from the mean of the measurements of three freshly prepared samples.

The neuroprotective effect of GSEe on SH-SY5Y cells under oxidative stress induced by H2O2. The plots show the effects of various concentrations of GSEe on SH-SY5Y cell viability. (A) MTT assay. (B) LDH assay. The error bars represent the standard deviation from the mean of the measurements of three freshly prepared samples.

The antioxidant effects of GSEe, or Enovita®, in various cell-free assays. (A) DPPH radical scavenging assay, EC50 5.81 ± 0.11 µg/mL. (B) ABTS radical scavenging assay, EC50 11.91 ± 0.15 µg/mL. (C) FRAP assay. (D) ORAC assay. (E) HORAC assay. (F) Total phenolic content (TPC) Folin–Ciocalteau assay. (G) TAS assay. The error bars represent the standard deviation from the mean of the measurements of three freshly prepared samples. TEAC: Trolox Equivalent Antioxidant Capacity; GAE: gallic acid equivalents; GA: gallic acid.
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