Dihydroquercetin regulates HIF-1α/AKT/NR2B signalling to improve impaired brain function in rats with metabolic syndrome

Yang Fu; PeiPei Yuan; Mengnan Zeng; Qi Zhang; Ying Hou; Liyuan Gao; Yaxin Wei; Yajuan Zheng; Weisheng Feng; Xiaoke Zheng

doi:10.1016/j.heliyon.2024.e29807

Dihydroquercetin regulates HIF-1α/AKT/NR2B signalling to improve impaired brain function in rats with metabolic syndrome

Heliyon. 2024 Apr 28;10(9):e29807. doi: 10.1016/j.heliyon.2024.e29807. eCollection 2024 May 15.

Authors

Yang Fu^{1

2}, PeiPei Yuan^{1

2}, Mengnan Zeng^{1

2}, Qi Zhang¹, Ying Hou¹, Liyuan Gao¹, Yaxin Wei¹, Yajuan Zheng¹, Weisheng Feng^{1

2}, Xiaoke Zheng^{1

2}

Affiliations

¹ Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China.
² The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou 450046, China.

Abstract

Dihydroquercetin (DHQ) is commonly used as a dietary additive, but its activity in improving brain injury with metabolic syndrome (MS) remains known. In present study, the MS rat model was induced using 10 % fructose water. The apoptosis rate of primary brain cells was detected. The HIF-1α/AKT/NR2B signalling pathway, levels of KEAP1/NRF2, HO-1 and NQO-1 were detected. In vitro experiments were performed using H₂O₂-stimulated PC-12 cells. The effect of DHQ on rates of cell survival and apoptosis were detected. After silencing HIF-1α, we further elucidate the mechanism of action of DHQ. The results indicated that DHQ reduced the hyperactivity and inhibited oxidative stress via increasing the levels of HIF-1α/AKT/NR2B signalling pathway, whereas regulated KEAP1/NRF2 pathway. In vitro experiments showed that the HIF-1α plays an important role in this process. Overall, DHQ may improve impaired brain function in rats with metabolic syndrome by regulating the HIF-1α/AKT/NR2B signalling pathway.

Keywords: Brain; Dihydroquercetin; HIF-1α/AKT/NR2B; Hypertension; Metabolic syndrome.