The Ethanol Extract of Zingiber zerumbet Attenuates Streptozotocin-Induced Diabetic Nephropathy in Rats

Abstract

The ethanol extract from the rhizome of Zingiber zerumbet (L.) Smith (EEZZR) has been indicated to possess an insulin-like property by ameliorating hyperglycemia in diabetes. We aimed to investigate whether EEZZR exerts an ameliorative effect on renal damage in diabetes induced by streptozotocin (STZ). Diabetic rats were treated orally with EEZZR (200 and 300 mg kg(-1) per day) or metformin (100 mg kg(-1) per day) for 8 weeks. The plasma glucose, creatinine, and blood urea nitrogen as well as urine protein levels and the ratio of kidney weight to body weight were significantly elevated in diabetic rats. EEZZR displayed similar characteristics to those of metformin in reducing hyperglycemia and renal dysfunction in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following the treatment with EEZZR. In addition, the protein expressions of renal nephrin and podocin in diabetic rats were significantly increased following the treatment with EEZZR. The AMP-activated protein kinase (AMPK) protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. EEZZR treatment significantly rescued the AMPK phosphorylation compared to nontreated diabetic group. This study suggested that the renoprotective effects of EEZZR may be similar, with the action of metformin, to the prevention of AMPK dephosphorylation and upregulate the expressions of renal nephrin and podocin.

Figure 1

(a) Representative photomicrographs (original magnification, 400x) of PAS-stained kidney sections, (b) glomerular volume, and (c) expansion of matrix index expressed as a quantitative estimate score in experimental groups. STZ-diabetic rats were dosed by oral gavage once per day for eight weeks with 100 mg kg⁻¹  per day metformin (STZ + Met), 200 mg kg⁻¹ per day EEZZR (STZ + EEZZR 200), or 300 mg kg⁻¹ EEZZR (STZ + EEZZR 300). Normal or STZ-diabetic rats receiving vehicle treatment were given the same volume of vehicle (distilled water) used to dissolve the test medications. Values (mean ± SD) were obtained for each group of 4 animals. ^b P < .01 compared to the values of vehicle-treated normal rats (normal + vehicle). ^c P < .05 and ^d P < .01 compared to the values of vehicle-treated STZ-diabetic rats (STZ + vehicle), respectively.

Figure 2

Effects of treatments on protein expressions of renal nephrin and podocin in the renal tissues of STZ-diabetic rats. STZ-diabetic rats were dosed by oral gavage once per day for eight weeks with 100 mg kg⁻¹ per day metformin (STZ + Met), 200 mg kg⁻¹ per day EEZZR (STZ + EEZZR 200), or 300 mg kg⁻¹ EEZZR (STZ + EEZZR 300). Normal or STZ-diabetic rats receiving vehicle treatment were given the same volume of vehicle (distilled water) used to dissolve the test medications. Values (mean ± SD) were obtained for each group of 4 animals. ^a P < .05 and ^b P < .01 compared to the values of vehicle-treated normal rats (normal + vehicle). ^c P < .05 and ^d P < .01 compared to the values of vehicle-treated STZ-diabetic rats (STZ + vehicle), respectively.

Figure 3

Effects of treatments on protein expression and phosphorylation of AMPK in the renal tissues of STZ-diabetic rats. STZ-diabetic rats were dosed by oral gavage once per day for eight weeks with 100 mg kg⁻¹ per day metformin (STZ + Met), 200 mg kg⁻¹ per day EEZZR (STZ + EEZZR 200), or 300 mg kg⁻¹ EEZZR (STZ + EEZZR 300). Normal or STZ-diabetic rats receiving vehicle treatment were given the same volume of vehicle (distilled water) used to dissolve the test medications. Values (mean ± SD) were obtained for each group of 4 animals. ^a P < .05 and ^d P < .01 compared to the values of vehicle-treated normal rats (normal + vehicle). ^c P < .05 and ^d P < .01 compared to the values of vehicle-treated STZ-diabetic rats (STZ + vehicle), respectively.