Naringin Protects Against High Glucose-Induced Human Endothelial Cell Injury Via Antioxidation and CX3CL1 Downregulation

Abstract

Background/Aims: The induction of endothelial injury by hyperglycemia in diabetes has been widely accepted. Naringin is a bio-flavonoid. Some studies showed that naringin alleviates diabetic complications, but the exact mechanisms by which naringin improves diabetic anomalies are not yet fully understood. The aim of this research was to study the protective effect of naringin on high glucose-induced injury of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were cultured with or without high glucose in the absence or presence of naringin for 5 days. The expression of CX3CL1 was determined by quantitative real-time RT-PCR (qPCR) and western blot. The cellular bioenergetic analysis oxygen consumption rate (OCR) was measured with a Seahorse Bioscience XF analyzer. Results: The production of reactive oxygen species (ROS), the expression of CX3CL1 and the level of AKT phosphorylation were increased in HUVECs cultured with high glucose compared with controls. However, naringin rescued these increases in ROS production, CX3CL1 expression and AKT phosphorylation. Nitric oxide (NO) production and OCR were lower in the high glucose group, and naringin restored the changes induced by high glucose. Molecular docking results suggested that Naringin might interact with the CX3CL1 protein. Conclusion: Naringin protects HUVECs from high-glucose-induced damage through its antioxidant properties by downregulating CX3CL1 and by improving mitochondrial function.

Human chorionic villous mesenchymal stem/stromal cells protect endothelial cells from injury induced by high level of glucose

“…EDN1 [ 50 , 51 ], TYMP [ 52 ], PROCR [ 53 ], F2R [ 35 , 53 ], TGFB1 [ 54 ], BCL2L1 [ 55 ], MMP1 [ 56 ], KDR [ 57 ], SPHK1 [ 58 ], TNFSF10 [ 59 ]) (Tables 2 and 5 ). Finally, pMSCs reduced glucose-treated endothelial cell expression of genes that induce their apoptosis ( FASLG [ 60 ]), injury ( ENG [ 48 ], CX3CL1 [ 61 ], F3 [ 62 ], THBD [ 62 ], AGTR1 [ 63 ]), and inflammation ( IL3 [ 64 ], ALOX5 [ 65 ], FLT1 [ 66 ]) (Tables 2 and 5 ). These data further support pMSCs having a beneficial effect on multiple endothelial cell functions in the presence of glucose.…”

Didymin prevents hyperglycemia-induced human umbilical endothelial cells dysfunction and death

“…Impairment of endothelium-dependent vasorelaxation is also caused by a loss of NO activity in the vessel walls [63]. Antioxidants such as curcumin and naringin have been shown to restore NO levels and improve endothelial dysfunction in vitro and in vivo [67, 68]. We have found that treatment with didymin increased HG-depleted eNOS protein expression and restored NO levels, suggesting that by restoring NO levels didymin could improve endothelial dysfunction.…”

“…Several lines of evidence suggest that hyperglycemia-induced changes in metabolism and signaling have been linked to the increased formation of ROS and AGEs, which further induces the redox-sensitive transcription factors such as NF-κB that transcribe several cytokines, adhesion molecules, and growth factors and leads to endothelial cell activation [66–68]. Our data showed that pre-treatment of HUVECs with didymin decreased the HG-induced NF-κB activation, which was accompanied by decreased translocation of p65 to the nucleus.…”

Effects and Underlying Mechanisms of Bioactive Compounds on Type 2 Diabetes Mellitus and Alzheimer’s Disease

“…Naringin, a flavonoid mostly found in grape fruit and related citrus species, has been reported for its antioxidant, anti-inflammatory, and antihyperglycemic properties [158, 159]. Recently, several new investigations indicated that naringin could improve T2DM and mitigate the severity of T2DM complications [159–161], and the underlying mechanism has been elucidated. In NA/STZ-induced type 2 diabetic rats, naringin produced a significant amelioration of the serum glucose level and lipid profile, such as LDL-cholesterol, LDL, and free fatty acids (Table 3) [159].…”

“…For instance, Chen et al [160] reported that naringin inhibited the high glucose-induced inflammatory reaction by mediating the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the rat mesangial cell. Furthermore, Li et al [161] indicated that naringin protected the human endothelial cell against high glucose-induced damage through inhibition of oxidation, downregulation of the chemokine (C-X3-C motif) ligand 1 (CX3CL1), and improvement of mitochondrial function (Table 2).…”