Curcumin Alleviates Oxygen-Glucose-Deprivation/Reperfusion-Induced Oxidative Damage by Regulating miR-1287-5p/LONP2 Axis in SH-SY5Y Cells

Abstract

Oxidative stress-induced neuronal damage is a main cause of ischemia/reperfusion injury. Curcumin (Cur), the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric), exhibits excellent antioxidant effects. Previous studies have indicated that miR-1287-5p was downregulated in patients with ischemic stroke. Additionally, we predicted that Lon Peptidase 2, Peroxisomal (LONP2), which is involved in oxidative stress regulation, is targeted by miR-1287-5p. The aim of the current study is to investigate the effect of Cur on ischemia/reperfusion damage and its underlying mechanism. To mimic ischemia/reperfusion damage environment, SH-SY5Y cells were subjected to oxygen-glucose-deprivation/reperfusion (OGD/R). OGD/R treatment downregulated miR-1287-5p and upregulated LONP2 in SH-SY5Y cells, but Cur alleviated OGD/R-induced oxidative damage and reversed the effect of OGD/R on the expression of miR-1287-5p and LONP2. Furthermore, we confirmed the interactive relationship between miR-1287-5p and LONP2 (negative regulation). We revealed that miR-1287-5p overexpression alleviated OGD/R-induced oxidative damage alleviation, similar to the effect of Cur. MiR-1287-5p inhibition accentuated OGD/R-induced oxidative damage in SH-SY5Y cells, which was reversed by Cur. The expression of LONP2 in OGD/R-treated SH-SY5Y cells was decreased by miR-1287-5p overexpression and increased by miR-1287-5p inhibition, and Cur counteracted the increase in LONP2 expression induced by miR-1287-5p inhibition. In conclusion, we suggest that Cur alleviates OGD/R-induced oxidative damage in SH-SY5Y cells by regulating the miR-1287-5p/LONP2 axis. The findings provide a theoretical basis for the clinical application of curcumin.

Curcumin protects PC12 cells from a high glucose-induced inflammatory response by regulating the miR-218-5p/TLR4 axis

“…It has been suggested that curcumin can alleviate oxidative damage by regulating the miR-1287-5p/LONP2 axis in SH-SY5Y cells. [22] Based on the evidence above, curcumin may exhibit a neuroprotective effect by regulating miR-218-5p in the high glucose (HG)-induced inflammatory response in DN. In this study, we determined the protective effects of curcumin on the high glucose-induced cell inflammatory response in cultured pheochromocytoma cells (PC12 cells), which were derived from a pheochromocytoma of the rat adrenal medulla. This model is frequently used to study the underlying mechanisms of glucose neurotoxicity.…”

“…It has been suggested that curcumin can alleviate oxidative damage by regulating the miR-1287-5p/LONP2 axis in SH-SY5Y cells. [ 22 ] Based on the evidence above, curcumin may exhibit a neuroprotective effect by regulating miR-218-5p in the high glucose (HG)-induced inflammatory response in DN.…”

Mechanisms Underlying Curcumin-Induced Neuroprotection in Cerebral Ischemia

“…Curcumin, as an antioxidant, accelerates the removal of ROS by activating the antioxidant enzymes and inhibiting the brain tissue damage induced by oxidative stress ( Vajragupta et al, 2003 ; Namgyal et al, 2021 ). The antioxidative effect of curcumin in cerebral ischemia has been widely explored, and it has been noted that curcumin could partially exert neuroprotection by alleviating oxidative stress-induced injury post-stroke ( Rathore et al, 2008 ; Mukherjee et al, 2019 ; Zhang et al, 2021 ). It was previously reported that pretreatment and posttreatment administration of curcumin both improved the antioxidative ability of the injured neurons ( Wu et al, 2015 ), while immediate and delayed (24 h after ischemia) treatments with curcumin both prevented ischemia-induced neuronal damage and oxidative insult, indicating the wide range time window of curcumin treatment in cerebral ischemia ( Al-Omar et al, 2006 ).…”

“…Various signaling pathways are involved in curcumin-induced antioxidation. For example, curcumin could alleviate the oxidative damage by regulating the miR-1287-5p/LONP2 axis and miR-7/RelA p65 axis in an OGD/R model ( Xu H. et al, 2019 ; Zhang et al, 2021 ). Another study described that dienone monocarbonyl curcumin analogs protected the cellular growth by eliminating ROS generation by activating the Nrf2/HO-1 signaling pathway ( He et al, 2021 ).…”

Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1

“…Ischemic-reperfusion (IR)-induced vascular cell death, which induces dysregulation of vascular reactivity, is a key contributor to mortality and morbidity in ischemic diseases, including myocardial IR injury, cerebral IR injury, and postoperative IR injury ( Pan et al, 2021 ; Zhang et al, 2021 ). Endothelial cells (ECs) line the intimal layer of blood vessels and play an important role in maintaining vascular homeostasis.…”