الفهرس 
Diabetes mellitusOnly 14 pages are availabe for public view
 |  | from | 207 |  |  |
| | | from | 207 | | |
Abstract
Diabetes mellitus (DM) is a metabolic disorder characterized by high level of blood glucose. The main types of DM are: type-1 and type-2. Diabetes ranks third in prevalence after cardiovascular diseases and cancer. The overall prevalence of diabetes is approximately 6% of the population, of which 90% is type-2. Moreover, diabetes without proper treatments can cause many complications. Type-2 (insulin-independent) diabetes is a hetero-geneous disorder of insulin resistance (IR) and pancreatic -cell dysfunction. IR plays a key role in the pathophysiology of type-2 diabetes; it is characterized by complex interactions between genetic determinants, inflammation and reactive oxygen species.
Recently, the “World Health Organization” has encouraged the use of medicinal plants to treat diabetes, especially in countries where conventional treatment of diabetes seems expensive. The present study aimed to evaluate and compare the modulatory effects of two different doses of pomegranate seed juice (PSJ, 100 and 300 mg/kg body weight) and punicalagin (PCG, one of PSJ active components, 2.6 and 7.8 mg/kg body weight) given orally (by gavage) and daily for 6 weeks on experimentally-induced type-2 diabetes in Wistar male albino rats by intraperitoneal injection of streptozotocin (STZ, 80 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). In addition, the study extended to detect any side effects for the PSJ and PCG.The results of the present study showed that the diabetic control group had a significant decrease (P<0.05-0.001, compared with the non-diabetic control group) in the body weight, muscle relative weight, serum insulin level, the hepatic antioxidant defence system (reduced glutathione, GSH, level and the activities of catalase, CAT; glutathione peroxidase, GPx; glutathione reductase, GR; glutathione S-transferase, GST; and superoxide dismutase, SOD). While, it showed a significant increase (P<0.01-0.001, compared with the non-diabetic control group) in the level of serum glucose and tumour necrosis factor-alpha (TNF-α), the percentage of glycated haemoglobin (HbA1c), IR index, the activity of serum markers of liver injury (ALAT and ASAT), hepatic lipid peroxidation, and hepatic nitric oxide (NOx) level. Moreover, the diabetic control group showed a down-regulation in the expression of hepatic insulin receptor substrate-1 (IRS-1, fold change = 0.32) and upregulation in the expression of hepatic c-Jun N-terminal kinase (JNK, fold change = 2.90) compared with the non-diabetic control group. Diabetic groups that received PSJ, especially at the high dose, had a significant increase (P<0.05-0.001, compared with the diabetic control group) in the body weight gain, muscle relative weight, serum insulin level, hepatic GSH concentration and the activity of the hepatic antioxidant enzymes (CAT, GPx, GR, GST and SOD). In addition, PSJ significantly decreased the food intake, serum glucose level, the percentage of HbA1c, IR index, the activity of serum transaminases (ALAT and ASAT), serum TNF-α level, and the hepatic lipid peroxidation as well as NOx level in diabetic rats (P<0.01-0.001, compared with the diabetic control group). Moreover, it significantly upregulated the hepatic IRS-1 expression (fold change = 2.49) and significantly downregulated the hepatic JNK expression (fold change = 0.53) in diabetic rats.
Also, the low dose of PCG improved some parameters in diabetic rats; it significantly increased (P<0.01-0.001, compared with the diabetic control group) the body weight gain, muscle relative weight, serum insulin level, the activity of some hepatic antioxidant enzymes (CAT, GR and SOD). In addition, it significantly decreased the level of serum glucose, the percentage of HbA1c, IR index and the hepatic lipid peroxidation in diabetic rats (P<0.01-0.001, compared with the diabetic control group). However, it increased inflammation in diabetic rats as it significantly increased the level of hepatic NOx and serum TNF-α. On the contrary, diabetic rats received the high dose of PCG did not show a valuable antidiabetic activity, but had many unfavourable adverse effects as a significant increase (P<0.001, compared with the diabetic control group) in the food intake, serum TNF-α level, and hepatic lipid peroxidation, NOx level, and JNK expression (fold change = 5.47), as well as a significant decrease (P<0.001) in the hepatic SOD activity.
On the other hand, the results obtained in this study affirmed that treatment of adult male Wistar albino rats with PSJ especially at the high dose decreased the body weight gain in non-diabetic animals, which may be beneficial in obese patients. Also, it significantly improved the activity of some hepatic antioxidant enzymes (GPx and GR), upregulated the hepatic IRS-1 expression and significantly decreased the serum TNF-α level and hepatic lipid peroxidation. While, PCG especially at the high dose induced a significant increase in the hepatic lipid peroxidation, serum transaminases (ALAT and ASAT) activities, and serum TNF-α level that in turn resulted in the overexpression of hepatic JNK; these were accompanying by a significant decrease in the hepatic antioxidant defence system. Therefore, PCG showed toxic effects especially at the high dosage.
In conclusion, PSJ is more effective than PCG in alleviating diabetes, especially at the high dose. The superior antidiabetic, anti-inflammatory and antioxidant effects of PSJ (without noticed side effects) over PCG shown in the present study proved the benefits of using PSJ that contains multiple compounds with multifactorial effects and synergism compared with using a single purified active ingredients such as PCG.