The comparative ameliorating effects of an amorphous formula of curcumin and α-glycosyl isoquercitrin on hippocampal dysfunction in a rat gulf war illness model.

Authors

Qian Tang, Momoka Shobudani, Yuri Sakamaki, Yuri Ebizuka, Xinyu Zou, Mio Kobayashi, Tetsuhito Kigata, Mihoko Koyanagi, Tomohiro Nakao, Makoto Shibutani

Published in

Metabolic brain disease. Volume 41. Issue 1. Jun 25, 2026. Epub Jun 25, 2026.

Abstract

Brain dysfunction is a primary symptom of Gulf War illness (GWI). The present study investigated the effects of an amorphous formula of curcumin (CUR) and α-glycosyl isoquercitrin (AGIQ) on neurobehaviors and adult neurogenesis and following synaptic plasticity of produced neurons in the hippocampal dentate gyrus (DG) in a rat GWI model. Ten-week-old rats received GWI-related chemicals and restraint stress for 28 days; thereafter, animals were fed either a diet without supplement or mixed with 0.1% CUR or 0.5% AGIQ for 126 days. GWI treatment adversely affected behavioral endpoints, including novel object recognition, sucrose preference, novelty-suppressed feeding, and contextual fear conditioning. CUR ameliorated all these effects, while AGIQ caused anxiety-like behavior and improved fear extinction learning. GWI treatment downregulated NRF2-KEAP1 pathway-related genes in the DG; both phytochemicals reversed most of these changes. GWI treatment increased CD68⁺ and CD163⁺ microglia populations in the DG hilus; both phytochemicals reversed the increase of CD68⁺ microglia. In the neurogenic niche, GWI treatment decreased GFAP⁺ neural stem cells but increased DCX⁺ and PCNA⁺ cells, decreased hilar SST⁺ and GAD67⁺ GABAergic interneurons, and downregulated Pvalb. CUR reversed decreases in GFAP⁺ cell and SST⁺ interneuron numbers. Both phytochemicals increased VGLUT1 immunoreactivity, restored the VGLUT1/VGAT ratio, and upregulated Bdnf, Gria1, Gria2, Gria3, Slc17a7, Ptgs2, and Mapk1. AGIQ further increased COX2⁺ cell numbers and upregulated Grin2a, Grin2b, and Mapk3. In summary, both phytochemicals may have exerted antioxidant effects and modulated excitatory/inhibitory balance via glutamatergic signaling in GWI animals; CUR was superior to AGIQ at normalizing aberrant neurobehaviors and neurogenesis.

PMID:
42347851
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.