Ampelopsin inhibits high glucose‐induced extracellular matrix accumulation and oxidative stress in mesangial cells through activating the Nrf2/HO‐1 pathway

Abstract

Oxidative stress plays an important role in diabetic nephropathy (DN), which is a diabetic complication. Ampelopsin (AMP) is a natural flavonoid that has been found to possess antidiabetic and antioxidative activities. However, the effect of AMP on DN remains unclear. In this study, we aimed to evaluate the protective effect of AMP on glomerular mesangial cells (MCs) exposed to high glucose (HG). We found that AMP improved HG‐caused cell viability reduction in MCs. AMP significantly suppressed the intracellular ROS production and expression levels of ROS producing enzymes NADPH oxidase 2 (NOX2) and NOX4. Increased of NOX activity in HG‐stimulated MCs was suppressed by AMP. Pretreatment with AMP inhibited extracellular matrix (ECM) accumulation in HG‐stimulated MCs with decreased expression levels of fibronectin (FN) and collagen type IV (Col IV). Furthermore, AMP elevated the expression levels of nuclear Nrf2 and heme oxygenase‐1 (HO‐1), as well as increased the mRNA levels of Nrf2‐driven genes NAD(P)H dehydrogenase quinone‐1 (NQO‐1) and HO‐1 in HG‐treated MCs. Knockdown of Nrf2 reversed the protective effects of AMP against HG‐induced oxidative stress and EMC accumulation in MCs. In conclusion, these findings indicated that AMP protected MCs from HG‐induced oxidative damage and ECM accumulation, which might be mediated by Nrf2/HO‐1 pathway.

Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling

“…Moreover, resveratrol, curcumin, ampelopsin, and apigenin were shown to have attenuating effects against oxidative damage in various cellular models of kidney injury [109,110,119,126]. Besides, salidroside has anti-apoptotic effects in HG-treated mouse podocytes, showing therapeutic promise in the management of kidney disease [128].…”

Dihydromyricetin Acts as a Potential Redox Balance Mediator in Cancer Chemoprevention

“…9 Mediators of Inflammation (RAW264.7) cells, glomerular mesangial cells (MCs), and HEI-OC1 auditory cells have been successfully used to determine the protective effects of DHM in oxidative stress, and oxidative stress is generally created in cell lines by using H 2 O 2 free radicals, LPS, methylglyoxal, and sodium nitroprusside [4,41,47,55,[61][62][63][64][65][66][67].…”

“…In animal studies, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), and malondialdehyde (MDA) are commonly measured oxidative stress parameters to estimate the antioxidant capacity of DHM [13,[68][69][70]. The major antioxidant effects of DHM through the Nrf2/HO-1 pathway, the Nrf2/Keap1 pathway, and the ERK and Akt pathways [5,62,66,71], with an increase of DHM, significantly decreased the ROS levels in human umbilical vein endothelial cells (HUVECs) [71]. DHM exhibited an antioxidative power by activating superoxide dismutase (SOD) and the Nrf2/HO-1 signaling pathway or the Nrf2/Keap1 pathway [5,64].…”

“…DHM exhibited an antioxidative power by activating superoxide dismutase (SOD) and the Nrf2/HO-1 signaling pathway or the Nrf2/Keap1 pathway [5,64]. Recently, Dong et al found that DHM exhibited antioxidative effects through the inhibition of intracellular ROS production and expression levels of ROS producing the enzymes NADPH oxidase 2 (NOX2) and NOX4, the suppression of MDA levels, the enhancement of SOD, and the activation of the Nrf2/HO-1 signaling pathway [66]. In another study, Zhang et al determined the protective effects of DHM on HUVECs against sodium nitroprusside-(SNP-) induced oxidative damage and reported that DHM reduced ROS production and MDA levels, and increased SOD activity by activating the PI3K/Akt/FoxO3a signaling pathways in HUVECs [65].…”

The Role of Non-coding RNAs in Diabetic Nephropathy-Related Oxidative Stress

“…Superoxide derived from nicotinamide adenine dinucleotide phosphate oxidase (NOX) plays a key role in hyperglycemiaderived OS in DN; OS production by NOX mediates matrix accumulation and renal fibrosis in DN (117,118). In HG-treated MCs and the kidneys of streptozotocin (STZ)-induced diabetic rats, the expression of miR-25 is significantly reduced, while the mRNA and protein levels of NOX4 are increased (119).…”