Effect of eugenol on postoperative cognitive dysfunction in vascular dementia rats via the regulation of TXNIP/TRX-1/GPX4 pathway-mediated ferroptosis

doi:10.13418/j.issn.1001-165x.2026.1.10

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Chinese Journal of Clinical Anatomy ›› 2026, Vol. 44 ›› Issue (1) : 61-69. DOI: 10.13418/j.issn.1001-165x.2026.1.10

Effect of eugenol on postoperative cognitive dysfunction in vascular dementia rats via the regulation of TXNIP/TRX-1/GPX4 pathway-mediated ferroptosis

Li Lin¹, Zhang Feng², Lu Xiangyu¹, Dong Yan², Li Chao²*

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Abstract

Objective To investigate the effect of eugenol on postoperative cognitive dysfunction in vascular dementia (VD) rats via modulation of thioredoxin-interacting protein/thioredoxin-1/glutathione peroxidase 4 (TXNIP/TRX-1/GPX4) pathway-mediated ferroptosis. Methods The rats were randomly divided into control group, model group, low-dose eugenol group, high-dose eugenol group, high-dose eugenol+OE-NC group, and high-dose eugenol+OE-TXNIP group, with 12 rats in each group. Except for control group, VD models were constructed in all other groups. The water maze experiment was used to exam the cognitive function of rats. ELISA was used to detect the contents of malondialdehyde (MDA) and reduced glutathione (GSH) in hippocampal tissue. Nissl staining and HE staining were used to observe the morphology of neurons in hippocampal CA1 area. Prussian blue staining was used to observe iron deposition in hippocampal tissue. Immunohistochemistry was used to detect the expressions of ferroptosis protein GPX4 and solute carrier family 7 member 11 (SLC7A11). Western blot was used to detect the expression of proteins related to TXNIP/TRX-1/GPX4 pathway in hippocampal tissues. Results Compared with control group, the pathological damage of hippocampal tissue in model group was severe. The morphology of neuronal cells in hippocampal CA1 area was irregular, with obvious phenomena of cell edema and nuclear condensation, enlarged cell gaps, blurred boundaries, disordered arrangement, obvious neuronal loss, significant reduction of Nissl body, and increased deposition of iron particles. The rats of model group had increased average escape latency, and decreased number of crossing platforms (P<0.05). The content of MDA and the expression of TXNIP were increased, while the content of GSH and the expressions of SLC7A11, TRX-1, and GPX4 were decreased in model group (P<0.05). Compared with model group, hippocampal tissue and neuronal damage in CA1 area in low-dose eugenol group and high-dose eugenol group were significantly improved, iron particle deposition was reduced, the average escape latency was shortened, the number of crossing platforms increased. Meanwhile, MDA content and TXNIP expression were decreased. The content of GSH and the expressions of SLC7A11, TRX-1, and GPX4 were increased in two group (P<0.05). In addition, high-dose eugenol+OE-TXNIP group partially reversed the protective effect of eugenol on the hippocampal tissue. Conclusions Eugenol can improve postoperative cognitive dysfunction in VD rats and is associated with the inhibition of ferroptosis mediated by TXNIP/TRX-1/GPX4 pathway.

Key words

Eugenol / / / TXNIP/TRX-1/GPX4 pathway / / / Ferroptosis / / / Vascular dementia / Postoperative cognitive dysfunction

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Li Lin, Zhang Feng, Lu Xiangyu, Dong Yan, Li Chao. Effect of eugenol on postoperative cognitive dysfunction in vascular dementia rats via the regulation of TXNIP/TRX-1/GPX4 pathway-mediated ferroptosis[J]. Chinese Journal of Clinical Anatomy. 2026, 44(1): 61-69 https://doi.org/10.13418/j.issn.1001-165x.2026.1.10

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