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Peer-reviewedCC BY 4.0Molecules

Zingiberis Rhizoma Ethanol Extract Attenuates Recognition Memory Deficits and Neuroinflammation in a Mouse Model of Bilateral Common Carotid Artery Stenosis

  • Taeyoung Huh1
  • Chiyeon Lim2
  • Sehyun Lim3
  • Kyung-Min Kim1
  • Suin Cho4
4 affiliations
  1. 1Department of Korean Medicine, College of Korean Medicine, Dong-Eui University, Busan 47227, Republic of Korea
  2. 2Center for Advanced Medical Computing and Analysis, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
  3. 3School of Public Health, Far East University, Eumseong 27601, Republic of Korea
  4. 4Department of Korean Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
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Abstract

Chronic cerebral hypoperfusion (CCH), a key contributor to vascular dementia (VaD), causes white matter injury and neuroinflammation. We evaluated the neuroprotective effects of 6-gingerol-rich Zingiberis Rhizoma ethanol extract (ZRex) in a mouse bilateral common carotid artery stenosis (BCAS) model. BCAS-operated C57BL/6 mice received oral ZRex (30, 100, or 300 mg/kg, three times weekly). Spatial working memory, recognition memory, glial activation, oligodendrocyte and myelin markers, RNA sequencing (RNA-seq), and 6-gingerol molecular docking were evaluated. ZRex partially restored recognition memory in the novel object recognition test without altering Y-maze spatial working memory. BCAS significantly increased platelet-derived growth factor receptor alpha-positive cell counts, which ZRex restored toward sham levels. ZRex also markedly attenuated cluster of differentiation 68 immunoreactivity. RNA-seq identified 479 BCAS-responsive candidate genes (fold-change-filtered) and demonstrated that ZRex selectively restored downregulated transcripts. Molecular docking revealed the strongest predicted binding of 6-gingerol to Mup19 (Vina score: −9.4 kcal/mol), followed by Serpina3, Saa2, Mup1, and F10. Overall, ZRex attenuated BCAS-induced recognition memory deficits and neuroinflammation by modulating metabolic and inflammatory pathways, potentially mediated by direct 6-gingerol interactions with candidate targets. These findings support ZRex as a promising botanical candidate for VaD.

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Cite

BibTeXRIS
BibTeX
@article{huh2026zingiberis,
  title = {{Zingiberis Rhizoma Ethanol Extract Attenuates Recognition Memory Deficits and Neuroinflammation in a Mouse Model of Bilateral Common Carotid Artery Stenosis}},
  author = {Taeyoung Huh and Chiyeon Lim and Sehyun Lim and Kyung-Min Kim and Suin Cho},
  journal = {Molecules},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31203634},
  url = {https://www.mdpi.com/1420-3049/31/20/3634},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Zingiberis Rhizoma Ethanol Extract Attenuates Recognition Memory Deficits and Neuroinflammation in a Mouse Model of Bilateral Common Carotid Artery Stenosis
AU  - Taeyoung Huh
AU  - Chiyeon Lim
AU  - Sehyun Lim
AU  - Kyung-Min Kim
AU  - Suin Cho
PY  - 2026
DA  - 2026/10/01
JO  - Molecules
DO  - 10.3390/molecules31203634
UR  - https://www.mdpi.com/1420-3049/31/20/3634
AB  - Chronic cerebral hypoperfusion (CCH), a key contributor to vascular dementia (VaD), causes white matter injury and neuroinflammation. We evaluated the neuroprotective effects of 6-gingerol-rich Zingiberis Rhizoma ethanol extract (ZRex) in a mouse bilateral common carotid artery stenosis (BCAS) model. BCAS-operated C57BL/6 mice received oral ZRex (30, 100, or 300 mg/kg, three times weekly). Spatial working memory, recognition memory, glial activation, oligodendrocyte and myelin markers, RNA sequencing (RNA-seq), and 6-gingerol molecular docking were evaluated. ZRex partially restored recognition memory in the novel object recognition test without altering Y-maze spatial working memory. BCAS significantly increased platelet-derived growth factor receptor alpha-positive cell counts, which ZRex restored toward sham levels. ZRex also markedly attenuated cluster of differentiation 68 immunoreactivity. RNA-seq identified 479 BCAS-responsive candidate genes (fold-change-filtered) and demonstrated that ZRex selectively restored downregulated transcripts. Molecular docking revealed the strongest predicted binding of 6-gingerol to Mup19 (Vina score: −9.4 kcal/mol), followed by Serpina3, Saa2, Mup1, and F10. Overall, ZRex attenuated BCAS-induced recognition memory deficits and neuroinflammation by modulating metabolic and inflammatory pathways, potentially mediated by direct 6-gingerol interactions with candidate targets. These findings support ZRex as a promising botanical candidate for VaD.
SN  - 1420-3049
ER  -