Tier 3 — preclinical

SIRT6 activation relieves neuropathic pain by restoring Nrf2 signaling and inhibiting NLRP3 inflammasome

Xintong Hao, Junkang Leng, Jianjun Tan
Frontiers in Physiology 2026 17:1888004

Bibliography

PubMed
PMID 42625583
DOI
10.3389/fphys.2026.1888004
Funding
Supported by the General Hospital of the Yangtze River Shipping.

Study snapshot

DesignChronic constriction injury rat study with pharmacological SIRT6 activation and Nrf2 inhibition.
ModelMale Sprague-Dawley rats with chronic constriction injury.
Samplen=6 for molecular groups and n=8 for behavioral groups as reported.
InterventionUBCS039 20 mg/kg or MDL-800 10 mg/kg intraperitoneally on days 3-9 after injury; ML385 used for pathway testing.
Duration7 days of treatment after nerve injury with day-10 outcomes.
EndpointsMechanical hypersensitivity; Thermal hypersensitivity; Nrf2/HO-1; NLRP3 inflammasome; IL-1β; IL-18; Oxidative stress

What the study showed, in plain terms

In a rat nerve-injury model, UBCS039 and MDL-800 reduced pain-like behaviors, oxidative stress and NLRP3 inflammatory signaling. Blocking Nrf2 eliminated the MDL-800 benefit, supporting a SIRT6-Nrf2-NLRP3 pathway.

Key findings

Two pharmacological SIRT6 activators improved behavioral and molecular neuropathic-pain outcomes in rats, with Nrf2 inhibition abolishing the measured MDL-800 effects.

What this study can and cannot tell us

Animal study only; intraperitoneal synthetic activators rather than oral fucoidan; does not establish efficacy or safety for human neuropathic pain.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability