6-Gingerol, a Bioactive Compound of Ginger Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats by Regulating the Oxidative Stress and Inflammation

Abstract

The aim of present study is to investigate the role of 6-gingerol in ameliorating the renal injury in streptozotocin (STZ)-induced diabetic rats. The diabetes was induced by using a single dose of freshly prepared STZ (55 mg/kg body weight) intraperitoneally which causes the degeneration of pancreatic Langerhans islet β-cells. The diabetic rats were treated with oral gavage of 6-gingerol (10 mg/kg b.w.). The treatment plan was continued for 8 weeks successively and the body weight and fasting blood glucose levels were weekly checked. The biochemical parameters like lipid profile, kidney profile, antioxidant enzyme levels, lipid peroxidation and anti-inflammatory marker levels were investigated after the treatment plant. The pathological condition of kidneys was examined by haematoxylin-eosin (H&E) staining besides this analysis of NF-κB protein expression by immuno-histochemistry was performed. Some of the major parameters in diabetes control vs. normal control were reported as fasting blood glucose (234 ± 10 vs. 102 ± 8 mg/dL), serum creatinine (109.7 ± 7.2 vs. 78.9 ± 4.5 μmol/L) and urea (39.9 ± 1.8 vs. 18.6 mg/dL), lipid profile levels were significantly enhanced in diabetic rats. Moreover, diabetic rats were marked with decreased antioxidant enzyme levels and increased inflammatory markers. Treatment with 6-gingerol significantly restored the fasting blood glucose level, hyperlipidaemia, Malondialdehyde (MDA) and inflammatory marker levels, NF-κB protein expression and augmented the antioxidant enzyme levels in the kidneys of diabetic rats. The kidney damage was significantly normalized by the treatment of 6-gingerol and it provides an evidence that this novel compound plays a significant role in the protection of kidney damage. These findings demonstrate that 6-gingerol reduces lipid parameters, inflammation and oxidative stress in diabetic rats, thereby inhibiting the renal damage. Our results demonstrate that use of 6-gingerol could be a novel therapeutic approach to prevent the kidney damage associated with the diabetes mellitus.

Keywords: 6-gingerol; diabetes mellitus; inflammation; oxidative stress; renal damage.

Figure 1

(a) The initial and the final body weight of different groups of rats after 8 weeks of experimental design. The rats were equally divided into 4 groups, each group (n = 8). Data are represented as mean ± standard error of the mean (SEM). Groups: Normal control (NC); disease control (DC), i.e., STZ-treated group; treatment group (DC + 6-gingerol); positive control (PC) animal treated with STZ + glibenclamide; * p < 0.05 (significant difference of final b.w. between DC vs. NC) # p < 0.05 (significant difference of final b.w. between DC vs. DC + 6-gingerol). (b): The values of serum glucose in different groups of rats after 8 weeks of treatment. The rats were equally divided into 4 groups, each group (n = 8). Data are represented as mean ± standard error of the mean (SEM). Groups: Normal control (NC); disease control (DC), i.e., STZ-treated group; treatment group (DC + 6-gingerol); positive control (PC) animal treated with STZ + glibenclamide; * p < 0.05 (significant difference of final b.w. between DC vs. NC) # p < 0.05 (significant difference of final b.w. between DC vs. DC + 6-gingerol).

Figure 2

The lipid profile in different groups of rats after 8 weeks of continues treatment. The rats were equally divided into 4 groups, each group (n = 8). Data are presented as mean ± standard error of the mean (SEM). Groups: Normal control (NC); disease control (DC), i.e., STZ-treated group; treatment group (DC + 6-gingerol); positive control (PC) animal treated with STZ + glibenclamide; * p < 0.05 (significant difference of final b.w. between DC vs. NC) # p < 0.05 (significant difference of final b.w. between DC vs. DC + 6-gingerol).

Figure 3

The kidney function test profile (creatinine and urea) in different groups of rats after 8 weeks of treatment. The rats were equally divided into 4 groups, each group (n = 8). Data are presented as mean ± standard error of the mean (SEM). Groups: Normal control (NC); disease control (DC), i.e., STZ-treated group; treatment group (DC + 6-gingerol); positive control (PC) animal treated with STZ + glibenclamide; * p < 0.05 (significant difference of final b.w. between DC vs. NC) # p < 0.05 (significant difference of final b.w. between DC vs. DC + 6-gingerol).

Figure 4

(a, b): The lipid peroxidation (MDA) and antioxidant enzyme (CAT, SOD, GST and GSH) level in different groups of rats after 8 weeks of treatment. The rats were equally divided into 4 groups, each group (sample size = 8). Data are shown as mean ± standard error of the mean (SEM). Groups: Normal control (NC); disease control (DC), i.e., STZ-treated group; treatment group (DC + 6-gingerol); positive control (PC) animal treated with STZ + glibenclamide; * p < 0.05 (significant difference of final b.w. between DC vs. NC) # p < 0.05 (significant difference of final b.w. between DC vs. DC + 6-gingerol).

Figure 5

The inflammatory markers level in different groups of rats after 8 weeks of treatment. The rats were equally divided into 4 groups, each group (sample size = 8). Data are summarized as mean ± standard error of the mean (SEM). Groups: Normal control (NC); disease control (DC), i.e., STZ-treated group; treatment group (DC + 6-gingerol); positive control (PC) animal treated with STZ + glibenclamide; * p < 0.05 (significant difference of final b.w. between DC vs. NC) # p < 0.05 (significant difference of final b.w. between DC vs. DC + 6-gingerol).

Figure 6

Effect of gingerol in histopathological changes of kidney tissues. (a): Typical architecture of kidney in control animals. (b): STZ only treated kidney tissues showed infiltration of lymphocytes, thickened glomerular basement membranes and congestion. (c): Administration of 6-gingerol markedly mitigated the irregularities in the glomerular and tubular architecture and displayed mild congestion, (d): positive control (diabetic rats treated with glibenclamide) showing normal architecture (e): Animal group treated with gingerol only showed normal architecture of kidney. (Scale bar = 100 µm).

Figure 7

Masson trichrome staining. Masson’s trichrome staining was showing that (a): Normal kidney architecture showing no collagen deposition; (b): significant increase in collagen deposition in animals treated with STZ was noticed; (c): Following treatment with gingerol and STZ treated group collagen deposition was reduced as compared to the disease control group, (d): positive control (diabetic rats treated with glibenclamide) not showing any collagen deposition, (e): Gingerol-treated group only did not show deposition of collagen. (Scale bar = 100 µm).

Figure 8

(A) (a): The expression of TNF-α protein was not noticed in kidney of normal control group while (b): it showed intense expression in diabetic control group. Moreover, (c): diabetic groups treated with 6-gingerol, exhibited weak expression in diabetic group plus 6-gingerol group. (d): positive control (diabetic rats treated with glibenclamide) not showing any expression, (e): Gingerol-treated group only did not show any expression. (Scale bar = 100 µm). (B): represents the graphical representation of TNF-α expression. The expression pattern was high in the diabetic control as compared to the normal control group (** p < 0.01). The diabetic group treated with 6-gingerol showed low expression as compared to the diabetic control (* p < 0.05). The expression pattern of TNF-α in the positive control and 6-gingerol treated only was statistically insignificant as compared to the control group (p > 0.05).