Zerumbone, a tropical ginger sesquiterpene, ameliorates streptozotocin-induced diabetic nephropathy in rats by reducing the hyperglycemia-induced inflammatory response

Abstract

BackgroundZerumbone is one of the pungent constituents of Zingiber zerumbet (L) Smith (Zingiberaceae family). The aim of the present study was to examine the effects of zerumbone in rats with streptozotocin-induced diabetic nephropathy (DN).MethodsDiabetic rats were treated orally with zerumbone (20 or 40 mg/kg/day) for 8 weeks. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses.ResultsDiabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight, that were reversed by zerumbone. Zerumbone treatment was found to markedly improve histological architecture in the diabetic kidney. Hyperglycemia induced p38 mitogen-activated protein kinase activation, leading to increased infiltration of macrophages and increased levels of interleukin (IL)-1, IL-6 and tumor necrosis factor-α. All of the above abnormalities were reversed by zerumbone treatment, which also decreased the expression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, transforming growth factor-β1 and fibronectin in the diabetic kidneys.ConclusionsThe beneficial effect of zerumbone in rats with DN is at least in part through antihyperglycemia which was accompanied by inhibition of macrophage infiltration via reducing p38 mediated inflammatory response.

Zerumbone protects INS-1 rat pancreatic beta cells from high glucose-induced apoptosis through generation of reactive oxygen species

“…These studies, combined with our findings, support that the protective effect of zerumbone on high glucosetreated INS-1 cells is largely mediated through inactivation of p38 and JNK MAPKs. The inhibition of p38 MAPK activation by zerumbone has also been described in a rat model of streptozotocininduced diabetic nephropathy [32].…”

Comparative Renal Protective Effects of Canagliflozin and Telmisartan in a Rat Model of Diabetic Nephropathy

“…It has been noted that nicotinamide administration with streptozotocin affords partial β-cell protection, to provide a model of insulin-deficient, but not insulin-resistant, form of type 2 diabetes characterized by stable, moderate hyperglycemia, with 60 % loss of β-cell function [20]. This animal model was shown to develop kidney affection and exhibit features of diabetic nephropathy after 8 weeks of hyperglycemia [28].…”

“…Samples were examined under light microscope by a pathologist unaware of the treatment protocol. The glomerular matrix expansion index was scored in four levels from 0 to 4, as follows: 0, normal glomeruli; 1, matrix expansion occurred in up to 25 % of a glomerulus; 2, matrix expansion occurred in 25-50 % of a glomerulus; 3, matrix expansion occurred in 50-75 % of a glomerulus; and 4, matrix expansion occurred in 75-100 % of a glomerulus [28]. Scores were assigned for at least 30 glomeruli from kidney sections for each rat, and the means were calculated.…”

“…It has been noted that nicotinamide administration with streptozotocin affords partial β-cell protection, to provide a model of insulin-deficient, but not insulin-resistant, form of type 2 diabetes characterized by stable, moderate hyperglycemia, with 60 % loss of β-cell function [20]. This animal model was shown to develop kidney affection and exhibit features of diabetic nephropathy after 8 weeks of hyperglycemia [28].Current results showed that, after 8 weeks of hyperglycemia, diabetic rats developed significant impairment of renal function and histopathological alterations, associated with increased levels of some inflammatory, oxidant and apoptotic markers. Treatment of diabetic rats with either canagliflozin or telmisartan produced impressive dose-related reduction in the amount of albuminuria in parallel with the decrease in other renal function parameters.…”

Zerumbone, A Natural Cyclic Sesquiterpene, Promotes ABCA1-Dependent Cholesterol Efflux from Human THP-1 Macrophages

“…Zerumbone is a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith and has shown many biological activities such as anti-inflammatory, antihyperglycemic, antioxidative, and anticancer activities [5,6,7]. In RAW264.7 murine macrophages, zerumbone has been shown to suppress lipopolysaccharide (LPS)-induced inflammatory response [8].…”