Troxerutin attenuates cognitive decline in the hippocampus of male diabetic rats by inhibiting NADPH oxidase and activating the Nrf2/ARE signaling pathway

Gao,Ming; Kang,Yaxing; Zhang,Lihui; Li,Hongyan; Qu,Changhui; Luan,Xiaqing; Liu,Lijun; Zhang,Songyun

doi:10.3892/ijmm.2020.4653

Troxerutin attenuates cognitive decline in the hippocampus of male diabetic rats by inhibiting NADPH oxidase and activating the Nrf2/ARE signaling pathway

Authors:
- Ming Gao
- Yaxing Kang
- Lihui Zhang
- Hongyan Li
- Changhui Qu
- Xiaqing Luan
- Lijun Liu
- Songyun Zhang
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Affiliations: Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Endocrinology, The First Shijiazhuang Hospital, Shijiazhuang, Hebei 050011, P.R. China, Department of Endocrinology, The Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University, Lianyungang, Jiangsu 222042, P.R. China, Department of Gastroenterology, Pipeline Bureau Hospital of Langfang, Langfang, Hebei 065000, P.R. China, Department of Hematology, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067020, P.R. China
Published online on: June 19, 2020 https://doi.org/10.3892/ijmm.2020.4653
Pages: 1239-1248

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Abstract

Diabetes‑associated cognitive decline is a recently identified a potential complication of diabetes. The present study was designed to examine the effects of troxerutin, a potent antioxidant, on cognitive function in rats with streptozotocin‑induced diabetes and to further explore the potential underlying mechanisms. Cognitive functions were investigated by the Morris water maze test. The malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in the hippocampus were assessed as the parameters of oxidative stress. Subunits of the NADPH oxidase (NOX) expression and nuclear factor erythroid 2‑related factor 2/antioxidant responsive element (Nrf2/ARE) signaling pathway were detected to explore the potential underlying mechanisms. The water maze test revealed that troxerutin significantly improved cognitive impairment in diabetic rats. Troxerutin treatment attenuated oxidative stress in the hippocampus of diabetic rats, as evidenced by the decreased MDA level and the increased SOD activity. Moreover, troxerutin activated the Nrf2/ARE signaling pathway via Nrf2 nuclear translocation in the cells in the hippocampus of diabetic rats. Troxerutin elevated the expression levels of the antioxidant enzymes, heme oxygenase‑1 (HO‑1) and NAD(P)H:quinone oxidoreductase (NQO1), and decreased the expression levels of the NOX subunits, gp91phox, p47phox and p22phox. On the whole, these findings demonstrate that troxerutin exerts neuroprotective effects against diabetes‑associated cognitive decline by suppressing oxidative stress in the hippocampus of rats with streptozotocin‑induced diabetes. Troxerutin may thus prove to be a potential therapeutic medicine for the treatment of diabetes‑associated cognitive decline.

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