Curcumin Derivative Cur20 Attenuated Cerebral Ischemic Injury by Antioxidant Effect and HIF-1α/VEGF/TFEB-Activated Angiogenesis

Abstract

In this paper, a curcumin derivative Cur20 was synthesized for better hydrolytic stability, which showed a higher angiogenic effect on zebrafish model than curcumin. In order to reveal the potential effects on neuroprotection, a mouse model of vascular dementia (VaD) induced by permanent right common carotid artery occlusion (rUCCAO) was established. After two weeks of curcumin administration, the cognitive function of mice was detected by Morris water maze and Y maze. The alteration on oxidative injuries and morphological damage were also analyzed by reactive oxygen species, superoxide dismutase, GSH, malondialdehyde tests, and Nissl stain on cortex/hippocampus. The angiogenesis and related signal factors were evaluated as well. The results showed that Cur20 significantly attenuated the cognitive dysfunction and histopathological changes of the VaD mice with enhanced antioxidant system and angiogenesis. In addition, primary rat brain microvessel endothelial cells (rBMECs) with oxygen glucose deprivation (OGD) were applied to further verify the possible mechanisms of Cur20-induced angiogenesis. The results demonstrated that the proliferation effect and the activation of pro-angiogenesis factors such as HIF-1α, VEGF, and TFEB might contribute to the protection of ischemic injury. Based on the above, our conclusion is that Cur20 can be considered as a promising therapeutic strategy for VaD.

RETRACTED ARTICLE: F-box and WD repeat domain-containing 7 (FBXW7) mediates the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway to affect hypoxic-ischemic brain damage in neonatal rats

“…also reported that silencing FBXW7 in hypoxia reduces ubiquitinated HIF-1α levels to improve HIF-1α expression [ 13 ]. Additionally, Cur20 enhanced angiogenesis in model mice with cerebral ischemic injury by activating the HIF-1α/VEGF signaling pathway, notably attenuating cognitive dysfunction in mice [ 48 ]. As revealed by Rania G Abdel-Latif et al ., empagliflozin upregulates the expression of the HIF-1α/VEGF signaling pathway to reduce the cerebral infarction area and alleviate neuronal apoptosis and cerebral injury in I/R-injured rats [ 49 ].…”

The Neuroprotective Effects of Memantine, and Curcumin after Cerebral Ischemia-reperfusion Injury in Elderly Rats

“…13 Several groups have demonstrated that CUR can inhibit cerebral ischemia. 7,[21][22][23] However, there is much that has not yet been revealed regarding the underlying mechanisms. A recent study shows that curcumin has neuroprotective effects due to its antioxidant in detail.…”

“…24 Besides antioxidant anti-inflammatory effects of CUR, Zhang et al, showed that the expression of vascular endothelial growth factor (VGEF) protecting neurons from ischemic injury and improving synaptic plasticity was increased by Cur20 which is a CUR derivate. 23 Also, it's been reported that CUR is more effective in neuroprotection, especially when applied as nanoparticles. 8,25 Experimental models of ischemia showed that the route of administration of CUR also affects its activity.…”

Triad3A-Dependent TLR4 Ubiquitination and Degradation Contributes to the Anti-Inflammatory Effects of Pterostilbene on Vascular Dementia

“…A device composed of three arms was labeled as A, B, and C. The mice were subjected to the Y-maze task. 32 Mice were first placed at the center of the maze facing arm A. When the mouse was navigating the maze, the number and the order of arm entries were recorded for 8 min.…”