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.
Highlights
Zerumbone is one of the pungent constituents of Zingiber zerumbet (L) Smith (Zingiberaceae family)
Effects of treatments on blood glucose levels Eight weeks following the induction of diabetes, STZdiabetic rats exhibited a significant increase in fasting blood glucose compared to rats in the normal control group
Plasma insulin level in the STZ-diabetic rats was not modified by zerumbone or rosiglitazone repeatedly treatment because plasma insulin levels were 0.35 ± 0.19 and 0.41 ± 0.21 μU/ml in STZ-diabetic rats treated for eight weeks with zerumbone (40 mg/kg/day) or rosiglitazone
Summary
Zerumbone is one of the pungent constituents of Zingiber zerumbet (L) Smith (Zingiberaceae family). Monocyte chemotactic protein-1 (MCP-1) and intercellular adhesion molecule (ICAM-1), which make the monocytes/macrophages extravasculate from the blood-stream and attract to the kidney tissue, promote the development of DN [4,5]. The inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β play an important role in the development of renal hypertrophy and hyperfunction during the development of DN [6]. It may be a novel therapy strategy for DN to reduce the infiltration of inflammatory cells
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