Abstract
Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has shown promising therapeutic potential against diabetic cataracts, but whether this compound exerts beneficial effects on the other diabetic microvascular complications remains unclear. This study was carried out to examine effects of gigantol on high glucose-induced renal cell injury in cultured mouse kidney mesangial cells (MES-13). MES-13 cells were pretreated with gigantol (1, 5, 10 or 20 μmol/L) for 1 h followed by further exposure to high (33.3 mmol/L) glucose for 48 h. Gigantol concentration dependently enhanced cell viability followed by high glucose treatment in MES-13 cells. High glucose induced reactive oxygen species (ROS) generation, malondialdehyde production and glutathione deficiency were recoved in MES-13 cells pretreated with gigantol. High glucose triggered cell apoptosis via the the loss of mitochondrial membrane potential, depletion of adenosine triphosphate, upregulation of caspases 9 and 3, enhancement of cytochrome c release, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by gigantol. High glucose also induced activation of JNK, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in MES-13 cells, which were blocked by gigantol. The results suggest that treatment MES-13 cells with gigantol halts high glucose-induced renal dysfunction through the suppression of the ROS/MAPK/NF-κB signaling pathways. Our data are of value to the understanding the mechanism for gigantol, and would benefit the study of drug development or food supplement for diabetes and nephropathy.
Highlights
Hyperglycemia and several other symptoms are involved in the development of complications associated with diabetes [1]
Cell viability was approximately 52% in high glucose-cultured cells, whereas gigantol prevented cell death caused by high glucose in a concentration-dependent manner, with almost 93% of the cells surviving at 20 mmol/L of gigantol (Figure 1B)
The experiments were performed in triplicate and data are presented as mean ± standard deviation (SD) of five independent experiments (n = 5). a p < 0.05 and b p < 0.01 when compared to the normal glucose vehicle (Veh)-treated control group. c p < 0.05 and d p < 0.01 when compared to the high glucose vehicle-treated group
Summary
Hyperglycemia and several other symptoms are involved in the development of complications associated with diabetes [1]. It has been revealed that strict control of blood glucose significantly lowered the development and progression of DN in both type I and type II diabetes, several mechanisms have been proposed to explain diabetic renal disease by hyperglycemia [3]. The overproduction of intracellular oxidative stress in response to hyperglycemia can occur in mitochondria that trigger. DNA damage and leads to the apoptosis of renal cells [6,7]. Due to the fact that the multiple mechanisms involved in the development of DN, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN
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