# Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells.
> 水素水がSK-N-MC細胞においてAMPKを介したSirt1-FoxO3a経路を活性化しアミロイドβ誘発細胞毒性を軽減する機序の解明


## Abstract

Amyloid beta (Aβ) peptides, implicated in Alzheimer's disease pathogenesis, promote reactive oxygen species (ROS) accumulation that leads to mitochondrial dysfunction and apoptotic cell death. Using SK-N-MC neuronal cells, this study examined how hydrogen-rich water (HRW) counteracts Aβ-induced cytotoxicity. HRW was found to directly neutralize excess ROS, thereby reducing oxidative damage. Additionally, HRW activated AMP-activated protein kinase (AMPK), which in turn upregulated forkhead box protein O3a (FoxO3a) through a sirtuin 1 (Sirt1)-dependent mechanism. This signaling cascade suppressed Aβ-induced mitochondrial membrane potential loss and attenuated overall oxidative stress. These findings identify the AMPK–Sirt1–FoxO3a axis as a key pathway through which HRW exerts neuroprotective effects against Aβ toxicity.

### Mechanism

HRW activates AMPK, which upregulates FoxO3a via a Sirt1-dependent pathway, scavenging excess ROS and preventing Aβ-induced mitochondrial membrane potential loss and apoptotic cell death.

## Bibliographic

- **Authors**: Lin CL, Huang WN, Li H, Huang C, Hsieh S, Lai C, et al.
- **Journal**: Chem Biol Interact
- **Year**: 2015 (2015-10-05)
- **PMID**: [26271894](https://pubmed.ncbi.nlm.nih.gov/26271894/)
- **DOI**: [10.1016/j.cbi.2015.07.013](https://doi.org/10.1016/j.cbi.2015.07.013)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 26271894. https://h2-papers.org/en/papers/26271894
> **Source**: PubMed PMID [26271894](https://pubmed.ncbi.nlm.nih.gov/26271894/)