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

Tzeng TF, Liou SS, Chang CJ, Liu IM - Nutr Metab (Lond) (2013)

Bottom Line: Zerumbone treatment was found to markedly improve histological architecture in the diabetic kidney.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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy & Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, R,O,C. iml@mail.tajen.edu.tw.

ABSTRACT

Background: Zerumbone 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).

Methods: Diabetic 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.

Results: Diabetic 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus

The possible action mechanisms of zerumbone on the amelioration of DN in STZ-diabetic rats. Hyperglycemia induced p38 activation to augment the expression of ICAM-1and MCP-1, thereby enhanced the infiltration of monocytes and/or macrophages. The activated macrophages promoted the expression of inflammatory cytokines including TNFα, IL-1 and IL-6. All of the above abnormalities were reversed by zerumbone treatment. Zerumbone also decreased the expression of fibronectin, by reducing the TGF-β1 expression in the diabetic kidney.
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Figure 6: The possible action mechanisms of zerumbone on the amelioration of DN in STZ-diabetic rats. Hyperglycemia induced p38 activation to augment the expression of ICAM-1and MCP-1, thereby enhanced the infiltration of monocytes and/or macrophages. The activated macrophages promoted the expression of inflammatory cytokines including TNFα, IL-1 and IL-6. All of the above abnormalities were reversed by zerumbone treatment. Zerumbone also decreased the expression of fibronectin, by reducing the TGF-β1 expression in the diabetic kidney.

Mentions: In diabetic animal models, p38 activity rapidly increases in glomeruli and tubules after the induction of hyperglycaemia, and is also found in the accumulating kidney interstitial cells associated with advanced nephropathy [12,25]. Increased renal cortical p38 activity in diabetic rats could be attenuated by improved glycemic control [26]. Treatment with zerumbone also reduced the elevated levels of p38 in the kidneys of STZ-diabetic rats, suggesting that the renal protective effect of zerumbone might be also related with the modulation of p38 signal transduction to attenuate hyperglycemia-affected renal dysfunction. We thus concluded that attainment of good glycemic control by zerumbone treatment could abrogate the increased renal p38 pathway activation in diabetic rats and led to minimize risk of DN. A possible mechanism for the renoprotective effect of zerumbone in STZ-diabetic rats is indicated in Figure 6. Although the renoprotective effect of zerumbone is not as effective as that produced by the standard drug rosiglitazone, an agonist of the peroxisome proliferator-activated receptor γ, zerumbone may be a suitable therapeutic adjunct for the patients who are particularly sensitive to the thiazolidinediones-associated side effects [27].


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

Tzeng TF, Liou SS, Chang CJ, Liu IM - Nutr Metab (Lond) (2013)

The possible action mechanisms of zerumbone on the amelioration of DN in STZ-diabetic rats. Hyperglycemia induced p38 activation to augment the expression of ICAM-1and MCP-1, thereby enhanced the infiltration of monocytes and/or macrophages. The activated macrophages promoted the expression of inflammatory cytokines including TNFα, IL-1 and IL-6. All of the above abnormalities were reversed by zerumbone treatment. Zerumbone also decreased the expression of fibronectin, by reducing the TGF-β1 expression in the diabetic kidney.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818326&req=5

Figure 6: The possible action mechanisms of zerumbone on the amelioration of DN in STZ-diabetic rats. Hyperglycemia induced p38 activation to augment the expression of ICAM-1and MCP-1, thereby enhanced the infiltration of monocytes and/or macrophages. The activated macrophages promoted the expression of inflammatory cytokines including TNFα, IL-1 and IL-6. All of the above abnormalities were reversed by zerumbone treatment. Zerumbone also decreased the expression of fibronectin, by reducing the TGF-β1 expression in the diabetic kidney.
Mentions: In diabetic animal models, p38 activity rapidly increases in glomeruli and tubules after the induction of hyperglycaemia, and is also found in the accumulating kidney interstitial cells associated with advanced nephropathy [12,25]. Increased renal cortical p38 activity in diabetic rats could be attenuated by improved glycemic control [26]. Treatment with zerumbone also reduced the elevated levels of p38 in the kidneys of STZ-diabetic rats, suggesting that the renal protective effect of zerumbone might be also related with the modulation of p38 signal transduction to attenuate hyperglycemia-affected renal dysfunction. We thus concluded that attainment of good glycemic control by zerumbone treatment could abrogate the increased renal p38 pathway activation in diabetic rats and led to minimize risk of DN. A possible mechanism for the renoprotective effect of zerumbone in STZ-diabetic rats is indicated in Figure 6. Although the renoprotective effect of zerumbone is not as effective as that produced by the standard drug rosiglitazone, an agonist of the peroxisome proliferator-activated receptor γ, zerumbone may be a suitable therapeutic adjunct for the patients who are particularly sensitive to the thiazolidinediones-associated side effects [27].

Bottom Line: Zerumbone treatment was found to markedly improve histological architecture in the diabetic kidney.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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy & Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, R,O,C. iml@mail.tajen.edu.tw.

ABSTRACT

Background: Zerumbone 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).

Methods: Diabetic 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.

Results: Diabetic 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus