# Unraveling the neuroprotective mechanisms of elephant black garlic extract against beta amyloid peptide-induced neurotoxicity

**Authors:** Javiera Gavilan, Jessica Panes-Fernández, Aníbal Araya, Claudia Pérez-Manríquez, José Becerra, Patricio Varas, Gustavo Moraga-Cid, Gonzalo E. Yévenes, Jorge Fuentealba

PMC · DOI: 10.3389/fnut.2025.1725284 · Frontiers in Nutrition · 2026-01-16

## TL;DR

Chilean Elephant Black Garlic protects brain cells from damage caused by a key protein linked to Alzheimer's disease.

## Contribution

This study is the first to show that Chilean Elephant Black Garlic has unique compounds that protect neurons from amyloid-beta toxicity.

## Key findings

- Chilean Elephant Black Garlic prevents cell death caused by amyloid-beta oligomers in mouse hippocampal slices.
- It preserves synaptic proteins and brain-derived neurotrophic factor levels in neurons exposed to amyloid-beta.
- The extract maintains mitochondrial function by preserving membrane potential and ATP levels under amyloid-beta stress.

## Abstract

Chilean Elephant Black Garlic (Allium ampeloprasum) is a distinctive variety whose biological activity remains largely unexplored. Unlike conventional black garlic derived from Allium sativum, this preparation exhibits a markedly different chemical profile enriched in sulfur-containing metabolites such as 3H-1,2-dithiol-3-thione (D3T) and 4-methyl-1,2,3-trithiolane (TTL). These compounds are rarely detected in traditional black garlic extracts and may underlie the specific protective effects observed in this study. Consequently, the biological actions described here cannot be generalized to other black garlic preparations. We provide the first evidence that Chilean Elephant Black Garlic (BG) confers neuroprotection against the toxicity of soluble oligomers of amyloid-beta (SO-Aβ), a central pathogenic element of Alzheimer’s disease (AD) known to trigger synaptic dysfunction and mitochondrial impairment. In mouse hippocampal slices, BG prevented SO-Aβ-induced reductions in cell viability. Complementary experiments in cultured hippocampal neurons showed that BG preserved spontaneous calcium signaling and prevented SO-Aβ-mediated alterations in neuronal arborization. At the molecular level, BG restored the expression of synaptic proteins (SV2 and PSD-95) and maintained BDNF levels. Beyond synaptic protection, BG also preserved mitochondrial function under SO-Aβ challenge by maintaining mitochondrial membrane potential, intracellular ATP levels, and Mitofusin-1 expression. Altogether, these findings identify Chilean Elephant Black Garlic, as functional food, that represent an important source of bioactive compounds with properties capable of counteracting key neurotoxic mechanisms implicated in AD.

## Linked entities

- **Proteins:** SV2A (synaptic vesicle glycoprotein 2A), DLG4 (discs large MAGUK scaffold protein 4), BDNF (brain derived neurotrophic factor), MFN1 (mitofusin 1)
- **Chemicals:** 4-methyl-1,2,3-trithiolane (PubChem CID 529757)
- **Diseases:** Alzheimer’s disease (MONDO:0004975)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** AD (MESH:D000544), synaptic dysfunction (MESH:C536122), mitochondrial impairment (MESH:D028361), neurotoxic (MESH:D020258), toxicity (MESH:D064420)
- **Chemicals:** ATP (MESH:D000255), calcium (MESH:D002118), 4-methyl-1,2,3-trithiolane (-), sulfur (MESH:D013455)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Allium sativum (garlic, species) [taxon 4682], Allium ampeloprasum (leek, species) [taxon 4681]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12857319/full.md

## References

63 references — full list in the complete paper: https://tomesphere.com/paper/PMC12857319/full.md

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Source: https://tomesphere.com/paper/PMC12857319