Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats.

Diabetes mellitus is characterized by hyperglycemia and complications affecting the eye, kidney, nerve and blood vessel. We have previously demonstrated the occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded by a depletion in the tissue level of glutathione. In this study, when diabetic rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a significant reduction in blood glucose, total cholesterol and triglyceride levels. On the other hand, oxidative stress has been implicated in the pathogenesis of diabetes and its complications. It was found that treatment by ginsenoside Re restored the levels of both glutathione and malondialdehyde in the eye and kidney to those found in the control rats. This is the first report demonstrating ginsenoside Re has significant antioxidant efficacy in diabetes, and prevents the onset of oxidative stress in some vascular tissues. Our results demonstrated that ginsenoside Re could lower blood glucose and lipid levels, and exerts protective actions against the occurrence of oxidative stress in the eye and kidney of diabetic rats. Our data also provide evidence that ginsenoside Re could be used as an effective antidiabetic agent particularly in the prevention of diabetic microvasculopathy.

Altered expression of serum protein in ginsenoside Re-treated diabetic rats detected by SELDI-TOF MS.

Diabetes mellitus (DM) is now a global health problem, however, its pathogenesis has not yet been fully deciphered. Even though modern medicine has great contribution to the control and treatment of DM, it is still far from success to completely cure the disease. Panax ginseng C.A. Meyer (ginseng) is a well-recognized traditional Chinese medicine for treating DM in Asia. In this study, high throughput proteomic approach has been adopted to investigate the antidiabetic action of 2 weeks' ginsenoside Re (Re, a major component of ginseng) administration to streptozotocin-induced diabetic rats. Employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and bioinformatics, 432 cluster peaks were detected in the samples, among them 293 potential biomarkers were found to have significant differentiations between the DM and control normal rats. When the Re-treated diabetic rats were compared to the untreated ones, a protein peak was detected to have significant alteration corresponding to Re treatment. This specific protein was found to match with C-reactive protein (CRP) in the protein database, and was subsequently validated by ELISA. This is the first study demonstrated that CRP could be altered by Re treatment, indicating that Re may improve diabetes and its complications by alleviation of inflammation.

Potential biomarkers found by protein profiling may provide insight for the macrovascular pathogenesis of diabetes mellitus.

Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.

Differential expression of proteins in kidney, eye, aorta, and serum of diabetic and non-diabetic rats.

Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C-reactive protein (CRP) in the Swiss-Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease.

Alterations in antioxidant enzyme activities in the eyes, aorta and kidneys of diabetic rats relevant to the onset of oxidative stress.

Profound changes in antioxidant enzyme activities were observed in a number of vascular tissues during the development of streptozotocin-induced diabetes in rats. In the eyes, there was an increase in superoxide dismutase activity at week 4 of diabetes. However, no difference in superoxide dismutase activity was observed between the control and diabetic animals at week 8. On the other hand, the diabetic state did not seem to affect the catalase activity in the eyes. There was a generalized increase in catalase activity of the eyes from week 4 to week 8 irrespective of the diabetic state. For glutathione peroxidase in the eyes, a decreased activity was observed in the diabetic animals at week 8, but not in week 4. A different pattern of enzyme activity changes was observed in the aorta where an increase in superoxide dismutase activity was observed in the diabetic group at week 4 but not in week 8. On the other hand, an increase in catalase activity was observed only at week 8 but not at week 4. Whereas there was no observed difference between the control and diabetic animals in glutathione peroxidase activity in the aorta, except for a generalized decrease from week 4 to week 8 in both groups of animals. In big contrast to the eyes and aorta where an increase in superoxide dismutase activity was observed at week 4 of diabetes, no change in kidney superoxide dismutase activity was noted at week 4 and a decrease was observed at week 8. A similar pattern of enzyme activity changes was observed for glutathione peroxidase in the kidneys. The catalase activity in the kidneys was not affected at all by the diabetic state at both week 4 and week 8. These results clearly demonstrate the active involvement of these antioxidant enzymes during the development of diabetes, and could be rationalized by the differential response of the tissues towards the different extent of oxidative stress imposed by the diabetic state on the different tissues.

Redox changes precede the occurrence of oxidative stress in eyes and aorta, but not in kidneys of diabetic rats.

Almost all diabetic complications are known to be associated with vascular dysfunctions of different tissues. Oxidative stress, on the other hand, has been implicated in the pathogenesis of diabetes mellitus. Therefore in the present study we have investigated the correlation between redox status and oxidative stress in the eyes, aorta and kidneys of streptozotocin (STZ)-induced diabetic rats. Glutathione (GSH), the primary endogenous antioxidant, and malondialdehyde (MDA), a marker of oxidative stress, were measured in these tissues of diabetic rats at different time points after STZ injection. Our results showed that GSH was reduced significantly in both the eyes and aorta of diabetic rats 8 weeks after STZ injection (43% and 66% of the control, respectively). Furthermore, the depletion of GSH occurred from the first week after STZ injection, and the level remained low as compared with the control rats (both week 1 and week 8: 43% and 66% of the control in the eyes and aorta, respectively). MDA was not increased until week 8 onwards after STZ-injection (177% and 93% of the control in the eyes and aorta, respectively). These changes, however, were not found in the kidneys, in which the GSH was slightly increased and MDA remained comparable to the control rats. These results indicate different tissues respond differently to high glucose conditions as redox changes and oxidative stress occurred only in the eyes and aorta but not in the kidneys of diabetic rats. In addition, the onset of oxidative stress is preceded by a depletion of GSH and probably an exhaustion of the antioxidant defense system. Furthermore, administration of Vitamin E was found to normalize MDA levels in the eyes and aorta but not in the kidneys of diabetic rats. In summary, our results suggest that the underlying mechanism in developing diabetic complications in the eyes and aorta involves the occurrence of oxidative stress, which may not be the case in diabetic kidneys. In addition, Vitamin E may prevent the development of diabetic complications in the eyes and aorta by reducing lipid peroxidation and oxidative damage in the cells.