# Acetylcholinesterase Inhibition and Antioxidant Activity of DHA‐Disubstituted Phospholipids

**Authors:** Ernestina Garcia‐Quinto, Sabrina Sollecito‐Rovella, Victor M. Amador‐Luna, Lidia Montero, Gloria Fernandez‐Lorente

PMC · DOI: 10.1002/mnfr.70095 · Molecular Nutrition & Food Research · 2025-05-13

## TL;DR

This study shows that DHA-based phospholipids can inhibit an enzyme linked to Alzheimer's and act as antioxidants, offering potential for brain health.

## Contribution

The study demonstrates the acetylcholinesterase inhibition and antioxidant properties of 1,2-Di-DHA-PC phospholipids.

## Key findings

- 1,2-Di-DHA-PC significantly inhibits acetylcholinesterase enzyme activity.
- 1,2-Di-DHA-PC exhibits antioxidant capacity comparable to ascorbic acid.
- The phospholipids may cross the blood-brain barrier and offer neuroprotection.

## Abstract

Docosahexaenoic acid (DHA) is an essential fatty acid for the central nervous system. It plays a crucial role in brain health and the prevention of neurodegenerative diseases, particularly in its phospholipid form, which has greater bioavailability. Previous studies, conducted by our group, enabled the enzymatic synthesis of pure disubstituted DHA phospholipids (1,2‐Di‐DHA‐PC). In the present study, the inhibitory activities of 1,2‐Di‐DHA‐PC on acetylcholinesterase (AChE) and its antioxidant capacity were evaluated. The results showed that 1,2‐Di‐DHA‐PC exhibited significant inhibition of the AChE enzyme. Moreover, 1,2‐Di‐DHA‐PC showed antioxidant capacity compared to ascorbic acid, a natural antioxidant par excellence. These findings highlight the therapeutic potential of 1,2‐Di‐DHA‐PC in the treatment of neurodegenerative diseases and its ability to offer protection against the lipid peroxidation of the neuronal aging process, one of the main drivers of neurodegeneration, suggesting the need for further studies to confirm its clinical applicability.

1,2‐Di‐DHA‐PC phospholipids in nutraceutical form may cross the blood‐brain barrier and inhibit acetylcholinesterase (AChE) activity, with an efficacy similar to galantamine. This suggests their potential as neuroprotective agents in the treatment of Alzheimer's disease.

## Linked entities

- **Proteins:** ACHE (acetylcholinesterase (Yt blood group))
- **Chemicals:** docosahexaenoic acid (PubChem CID 445580), DHA (PubChem CID 15608515), ascorbic acid (PubChem CID 9888239), galantamine (PubChem CID 9651)
- **Diseases:** Alzheimer's disease (MONDO:0004975)

## Full-text entities

- **Genes:** ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}
- **Diseases:** neurodegeneration (MESH:D019636)

## Full text

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## Figures

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## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12280846/full.md

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Source: https://tomesphere.com/paper/PMC12280846