The Effect of Ginger (Zingiber officinale) on Oxidative Stress Status in the Small Intestine of Diabetic Rats

This Article


Article Information:

Group: 2008
Subgroup: Volume 6, Issue 3, Summer
Date: September 2008
Type: Original Article
Start Page: 144
End Page: 150


  • MH Khadem Ansari
  • Department of Biochemistry,Faculty of Medicine, Urmia University of Medical Sciences, Urmia, IR.Iran
  • M Karimipour
  • Department of Anatomy and Faculty of Medicine, Urmia University of Medical Sciences, Urmia, IR.Iran
  • S Salami
  • Department of Biochemistry,Faculty of Medicine, Urmia University of Medical Sciences, Urmia, IR.Iran
  • A Shirpoor
  • Department of Physiology,Faculty of Medicine, Urmia University of Medical Sciences, Urmia, IR.Iran


      Affiliation: Department of Physiology,Faculty of Medicine, Urmia University of Medical Sciences
      City, Province: Urmia,
      Country: IR.Iran


Oxidative stress is produced under diabetic con-ditions and possibly causes various forms of tis-sue damage in patients with diabetes. The aim of the study was to investigate the effect of ginger on the occurrence of oxidative stress in the small intestine of diabetic rats. Materials and Methods: Twenty-four male Wis-tar rats were divided into three groups: control group, nontreated diabetic group, and diabetic group treated with ginger powder as 5% of their daily food. After 6 weeks, lipid peroxidation, protein oxidation, superoxide dismutase (SOD), and catalase levels of the small intestine were measured. Results: Diabetes caused significant increase of small intestine lipid peroxidation, protein oxida-tion, and SOD levels and decrease of catalase ac-tivity. Lipid peroxidation and protein oxidation were attenuated after consumption of ginger in the diabetic rats, and increased catalase activity. Conclusions: These findings indicate that ginger, as an oxidant, improves diabetes induced oxidative stress and its complications through prevention of lipid peroxidation and protein oxidation.

Keywords: Diabetes. Ginger;Oxidative stress;Small intestine;Rat

Manuscript Body:


Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and insufficiency of secretion or action of endogenous insulin that frequently results in severe metabolic imbalances and pathological changes in many tissues1 Dysfunction of the gastrointestinal tract is common among diabetic patients.2 As many as 75% of patients visiting diabetes clinics report significant gastrointestinal symptoms.3 The intestinal mucosa is vulnerable to oxidative stress on account of the constant exposure to reactive oxygen species (ROS) generated by several conditions such as ischemia/ reperfusion, inflammatory bowel disease, surgical stress, and diabetes.4 Increased oxidative stress is important in the development and progression of diabetes and related complications. Excessively high levels of free radicals cause damage to cellular proteins, membrane lipids, and nucleic acids, and eventually cell death. Increased production of high levels of reactive oxygen–free radicals has been linked to glucose oxidation and non-enzymatic glycation of proteins, which contribute to the development of diabetic complications in many tissues.1The cellular antioxidant status determines the susceptibility to oxidative damage and is usually altered in response to oxidative stress.5The protective effects of exogenously administered antioxidants have been extensively studied in animal models in recent years. Several studies have shown that consumption of antioxidant vitamin and nutrient-rich antioxidants such as ginger decrease diabetic complications and improves the antioxidant system of the body.6Ginger (Zingiber officinale rhizome) is a widely used herbal medicine for the treatment of diseases, including those affecting the digestive tract.7 The anti–diabetic activity of ginger has been reported in streptozotocin–induced diabetic rats.8,9Considering reports of other studies that document occurrence of oxidative stress in the small intestine of diabetic rats, the present study aimed to investigate the effects of ginger, as an antioxidant, on diabetes-induced alterations enzymatic and oxidative components of the antioxidant defense systems in the small intestine mucosal layer of diabetic rats.


The mean body weight, blood glucose, HbAlc and total protein levels of the nontreated diabetic and ginger-treated groups are given in Table 1, compared with those of the control group.


Table1. Effect of ginger on body weight, blood glucose, HbAlc and total protein in control, diabetic and ginger treated diabetic group

Group Body weight (g) Blood glucose
HbAlc Total protein
small intestine
  Initial 6th week Initial 6th week Initial 6th week Initial 6th week
Control 268. 6±9. 8 274. 8±10. 8 146.5±15 151.0±12.0 5. 4±0. 1 4. 8±0. 6 NA 7. 0±0. 5
Diabetic 261. 8±24. 0 184. 8±15. 6 362.3±55.0 604.4±48.0a 8. 2±3. 1a 29. 9±2. 7a NA 7. 5±0. 5
259. 3±17. 8 194. 5±18. 9 345.2±25.0 380.3±65.0a,b 6. 2±0. 1b 6. 8±0. 9b NA 7. 4±0. 4

Data are expressed as mean ± SD; n=8; asignificant difference compared to control; bsignificant difference

compared to diabetic; NA: not applicable


The body weights of rats at the beginning of the study were similar in all groups. At the end of study, after 6 weeks, nontreated diabetic and ginger-treated diabetic rats showed weight loss. However, the body weight loss in ginger-treated rats was lower than that in nontreated diabetic rats.The blood glucose concentration of the ginger-treated diabetic group at the end of 6 wk decreased significantly compared with that of the nontreated diabetic group (P<0.05). As shown in Table 1, the HbAlc level was significantly higher in nontreated diabetic rats than in control (normal) rats (P<0.001), but it was normalized in the ginger-treated rats. The intestinal levels of total protein did not differ significantly between groups.Catalase activity in the nontreated diabetic group was significantly decreased compared with that in the other two groups (P<0.05). There was no significant difference between control and the ginger treated groups (Fig. 1a).The SOD activity in the nontreated diabetic group was significantly higher than in the control group (P<0.001), but, in comparison with ginger treated rats, the difference was not significant. However, the SOD activity in the ginger- treated group was significantly higher than that in the control group (P<0.01) (Fig. 1b). A significant increase in protein carbonyl content was seen in the nontreated diabetic group compared with the control (p<0.05) and ginger- treated group (P<0.001), but no significant difference was found between control and ginger-treated rats (Fig.1c). As shown in Fig. 1d, 8- isoprostane level was increased in the diabetic group as compared with the control group (P<0.001). In ginger-treated diabetic rats, 8– isoprostane was decreased significantly compared with nontreated diabetic rats (P<0.001), whereas in control rats, the difference was not significant.

Fig. 1. Biochemical markers of oxidative stress: a. catalase activity b. activity of superoxide dismutase
c. protein carbonyl content and d. level of 8 isoprostane



In this study, we evaluated the hypothesis that ginger powder prevents hyperglycemia – induced oxidative stress in the small intestine mucosa in STZ–induced type I diabetes in rats. The results proved the occurrence of oxidative damage in the small intestine during the experimental diabetes episode and also revealed that consumption of ginger can improve oxidative stress status with attenuation of lipid peroxidation, protein oxidation, lowering the blood glucose level.Lipid peroxidation may bring about protein damage and inactivation of membrane-bound enzymes, either through direct attack by free radicals or through chemical modification by its end products, malondialdehyde and 4–hydroxynonenal;14 It is also known to decrease the fluidity of the intestinal brush border membrane.15 Our results showed ginger significantly reduced the extent of lipid peroxidation, which confirmed the findings of other studies.8In this study, the levels of protein–bond carbonyls in the small intestine of non treated diabetic rats were significantly high. Measurement of protein carbonyl is the most widely utilized measure of protein oxidation.16 It has been proposed that carbonyl stress i.e., the increase in reactive carbonyl compounds derived from oxidative and non–oxidative reactions leads to increased chemical modification of proteins and at a later stage to oxidative stress and tissue damage. A deficit in the detoxification of carbonyl compounds by the enzymes of glyoxalase pathway and aldose reductase is believed to be partly responsible for carbonyl stress and consequent oxidative stress.17The diabetes-induced stimulation of intestinal mucosal growth is believed to be a response to elevated physiological demands. The accompanying increase in the transport of oxidizable compounds such as glucose, amino acids,18 and lipids,19 alongwith the increased synthesis of cholesterol and triglycerides20 and decreased utilization of glucose within the enterocyte,21 can lead to transient increases in the intracellular concentrations of these compounds. The free radicals generated by autoxidation of these compounds may have been responsible for the elevation in lipid peroxidation and protein oxidation.4 Our results showed that ginger significantly decreased protein oxidation compared with the nontreated diabetic group. The hypolipidemic effect of ginger has been shown by other investigators22. It is likely that the hypochlosterolemic effects of ginger stem from the inhibition of cellular cholesterol synthesis. Attenuation of cholesterol synthesis results in augmentation of LDL receptor activity, which leads to elimination of LDL from plasma.23 It is well established that elevation of LDL oxidation induces oxidative stress and resultant damage.
8-isoprostane is an oxidative stress marker24 and its level increases during diabetes. In this study the level of 8-isoprostane was significantly high but reduced levels were found in ginger treated rats.The HbAlc level in the ginger-treated group was significantly lower than that in the nontreated diabetic group. It has been showed that HbAlc level increases during diabetes25 and it is a marker which shows the degree of protein glycation.26 Administration of ginger to diabetic rats significantly decreased the level of glycosylated haemoglobin and this may be due to the decreased level of blood glucose.To avoid oxidative stress, antioxidant enzymes, such as catalase and SOD, play an important role in reducing oxidative stress.27 Hyperglycemia–induced oxidative stress plays a key role in the development of diabetes and its complications. There is currently no consensus regarding antioxidant enzyme levels in various organs during the diabetic diseased state. Whereas some studies measuring activities of SOD and catalase in diabetes mellitus show the reductions in levels of these enzymes, others report the increases in the activities of both enzymes with the STZ – induced diabetes. SOD catalyzes the conversion of superoxide radical to H2O2. It protects the cell against the toxic effect of superoxide radicals.28 In the present study, the activity of SOD was significantly high in the small intestine mucosa of the nontreated diabetic rats. The increased SOD activity might be another sign of the increased oxidative stress in the intestinal tissue. The amount of SOD activity in the ginger-treated group was lower than nontreated diabetic group, but the difference was not significant. Ginger might be a scavenger for the free oxygen radicals and it somewhat prevented the elevation of the activities of SOD enzyme in the small intestine of diabetic rats.Catalase activity decreased significantly in the nontreated diabetic rats compared with that in other groups. Consumption of ginger restored catalase activity to the level similar to that in control rats. Catalase is one of antioxidative factors involved in elimination of ROS29 and has a predominant role in controlling the concentration of H2O2.30 However, the increase in catalase activity in the small intestine of diabetic rats has been reported 4 and other investigators reported a lack of changes in the activity of intestinal catalase rats fed diets containing different fat supplement.31 Such different findings may depend on several factors, such as animal strain, duration of the experiment, severity of diabetes, and assay techniques used to determine of catalase activity. However, other investigators showed decrease of blood catalase activity in diabetic patients.29In conclusion, our results demonstrate that administration of ginger improves oxidative stress induced by type I diabetes by decreasing lipid peroxidation and protein oxidation as free radical generation sources and also by elevating the level of enzymes which implicated in the antioxidant defense system.It seems that further investigation with bigger sample sizes should be considered to find out the precise mechanism of ginger as an antioxidant and its functional bioactive materials.

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