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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

Effects of treatments on renal chemokines expression. (A) Representative immunoblots of protein expression of MCP-1 and ICAM-1 in renal tissues of STZ-diabetic rats treated for eight weeks with zerumbone (ZER) or rosiglitazone (RGZ). STZ-diabetic rats were dosed by oral gavage once daily for eight weeks with 20 mg/kg ZER (ZER 20), 40 mg/kg ZER (ZER 40) or 5 mg/kg RGZ (RGZ). Normal (normal + VEH) or STZ-diabetic rats receiving vehicle treatment (STZ + VEH) were administered the same volume of vehicle (VEH) used to dissolve test medications. (B) Ratio of MCP-1/β-actin or ICAM-1/β-actin is expressed as the mean with SD (n = 4 per group) in each column. ap < 0.01 and bp < 0.01 compared to vehicle-treated normal rats. cp < 0.05 and dp < 0.01 compared to vehicle-treated STZ-diabetic rats, respectively.
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Figure 3: Effects of treatments on renal chemokines expression. (A) Representative immunoblots of protein expression of MCP-1 and ICAM-1 in renal tissues of STZ-diabetic rats treated for eight weeks with zerumbone (ZER) or rosiglitazone (RGZ). STZ-diabetic rats were dosed by oral gavage once daily for eight weeks with 20 mg/kg ZER (ZER 20), 40 mg/kg ZER (ZER 40) or 5 mg/kg RGZ (RGZ). Normal (normal + VEH) or STZ-diabetic rats receiving vehicle treatment (STZ + VEH) were administered the same volume of vehicle (VEH) used to dissolve test medications. (B) Ratio of MCP-1/β-actin or ICAM-1/β-actin is expressed as the mean with SD (n = 4 per group) in each column. ap < 0.01 and bp < 0.01 compared to vehicle-treated normal rats. cp < 0.05 and dp < 0.01 compared to vehicle-treated STZ-diabetic rats, respectively.

Mentions: The renal MCP-1 and ICAM-1 proteins were 3.0 and 2.9 fold higher in STZ-diabetic rats compared with normal rats, respectively. These increases were ameliorated by 74.2 ± 5.1 and 58.7 ± 3.9%, respectively, after eight weeks of treatment with rosiglitazone (Figure 3). Treatment of STZ-diabetic rats with 40 mg/kg/day zerumbone for eight weeks resulted in a marked 58.8 ± 3.7 and 29.3 ± 2.9% reduction of renal MCP-1 and ICAM-1protein expression, respectively, compared with that in vehicle-treated counterparts (Figure 3).


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)

Effects of treatments on renal chemokines expression. (A) Representative immunoblots of protein expression of MCP-1 and ICAM-1 in renal tissues of STZ-diabetic rats treated for eight weeks with zerumbone (ZER) or rosiglitazone (RGZ). STZ-diabetic rats were dosed by oral gavage once daily for eight weeks with 20 mg/kg ZER (ZER 20), 40 mg/kg ZER (ZER 40) or 5 mg/kg RGZ (RGZ). Normal (normal + VEH) or STZ-diabetic rats receiving vehicle treatment (STZ + VEH) were administered the same volume of vehicle (VEH) used to dissolve test medications. (B) Ratio of MCP-1/β-actin or ICAM-1/β-actin is expressed as the mean with SD (n = 4 per group) in each column. ap < 0.01 and bp < 0.01 compared to vehicle-treated normal rats. cp < 0.05 and dp < 0.01 compared to vehicle-treated STZ-diabetic rats, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effects of treatments on renal chemokines expression. (A) Representative immunoblots of protein expression of MCP-1 and ICAM-1 in renal tissues of STZ-diabetic rats treated for eight weeks with zerumbone (ZER) or rosiglitazone (RGZ). STZ-diabetic rats were dosed by oral gavage once daily for eight weeks with 20 mg/kg ZER (ZER 20), 40 mg/kg ZER (ZER 40) or 5 mg/kg RGZ (RGZ). Normal (normal + VEH) or STZ-diabetic rats receiving vehicle treatment (STZ + VEH) were administered the same volume of vehicle (VEH) used to dissolve test medications. (B) Ratio of MCP-1/β-actin or ICAM-1/β-actin is expressed as the mean with SD (n = 4 per group) in each column. ap < 0.01 and bp < 0.01 compared to vehicle-treated normal rats. cp < 0.05 and dp < 0.01 compared to vehicle-treated STZ-diabetic rats, respectively.
Mentions: The renal MCP-1 and ICAM-1 proteins were 3.0 and 2.9 fold higher in STZ-diabetic rats compared with normal rats, respectively. These increases were ameliorated by 74.2 ± 5.1 and 58.7 ± 3.9%, respectively, after eight weeks of treatment with rosiglitazone (Figure 3). Treatment of STZ-diabetic rats with 40 mg/kg/day zerumbone for eight weeks resulted in a marked 58.8 ± 3.7 and 29.3 ± 2.9% reduction of renal MCP-1 and ICAM-1protein expression, respectively, compared with that in vehicle-treated counterparts (Figure 3).

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