ANTIDIABETIC, HYPOLIPIDEMIC AND ANTIOXIDANT ACTIVITIES AND PROTECTIVE EFFECTS OF PUNICA GRANATUM PEELS POWDER AGAINST PANCREATIC AND HEPATIC TISSUES INJURIES IN STREPTOZOTOCIN INDUCED IDDM IN RATS Original Article ENTSAR A. SAAD* 1 , MOHAMED M. HASSANIEN 2 , MAHA A. El-HAGRASY 1 , KHOLOUD H. RADWAN 1 1 Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt, 2 entsarsaad@gmail.com Chemistry Department, Industrial Education College, Beni-Suef University, Beni-Suef, Egypt Email: Received: 08 May 2015 Revised and Accepted: 01 Jun 2015 ABSTRACT Objective: There is a growing interest in traditional medicinal plants since they contain medicinally active products to remedy many diseases. Punica granatum (PG) has many medicinal applications. The aim of this study was to investigate the antidiabetic, hypolipidemic, antioxidant and hepato-pancreatic protective effects of PG peel powder (PGPP) on streptozotocin (STZ) induced diabetic rats. Methods: Male Swiss albino rats became diabetic with insulin-dependent diabetes mellitus (IDDM) after a single intravenous injection of STZ (50 mg/kg). IDDM-rats received either a daily oral dose of PGPP (200 mg/kg), or insulin for 20 days. On day 21, rats were sacrificed and levels of fasting blood glucose (FBG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, lipid profile, lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (TAC) were estimated. Histopathological studies of liver and pancreas were performed. Results: There was a significant elevation in FBG, AST, ALT activities, NO and LPO levels for induced IDDM. In contrast, albumin level, SOD activity, and TAC exhibited the significant decline. In addition, there was marked lipid profile disturbances, and histopathological changes of liver and pancreas. Following PGPP supplementation, the levels of all the above-mentioned factors were back to normal. Also, liver architecture and the size of an islets of Langerhans of the pancreas were almost back to normal. The effect of PGPP was more pronounced when compared with insulin. Conclusion: PGPP is an effective alternative for the treatment of IDDM through the regeneration of β cells of pancreas and via its strong antioxidant properties. Keywords: Diabetes, Lipids, Oxidative stress, Liver, Pancreas, β cells, Histopathology. INTRODUCTION Diabetes mellitus (DM) is considered as the most common endocrine disease and heterogeneous metabolic disorder; affecting 5% of the world’s population. It is characterized by insufficiency of insulin secretion and/or action, insulin resistance, and abnormal metabolism of glucose, lipid and protein. Globally, DM causes high mortality and is the second most common cause of death after cancer. It is known to cause a variety of complications such as renal failure, blindness, limb amputation, neurological complications, vascular complications of coronary artery disease, cerebrovascular disease and/or premature death [1, 2]. DM is categorized into several types the two major ones are type 1 and type 2. On the basis of etiology, the term type 1 and type 2 are widely used to describe insulin-dependent diabetes mellitus (IDDM) and noninsulin- dependent diabetes mellitus (NIDDM), respectively [3]. Although different types of oral hypoglycemic agents are available along with insulin for the treatment of DM, none offers complete glycemic control [2]. In addition, the side effects of taking insulin and oral hypoglycemic agents have brought about a growing interest among those patients for alternative traditional medicinal plants with antidiabetic activity [4]. Therefore, an investigation of such agents has become of great interest. The pomegranate, botanical name Punica granatum (P. granatum) is a fruit-bearing deciduous shrub or a small sized tree that belongs to the Punicaceae family [5]. Nowadays, it is widely cultivated throughout the Middle East, Northern and Tropical Africa, Central Asia, and drier parts of Southeast Asia [6]. Pomegranates may contain nearly three times antioxidants as green Tea [5]. Compared with the pulp, the inedible Punica granatum (PG) peel contains as much as three times the total amount of polyphenols, including condensed tannins and catechins, gallocatechins and prodelphinidins [7, 8]. The antioxidant capacity of PG peel extract is 10 times higher than the pulp extract [9]. PG has been used for thousands of years to cure a wide range of diseases across different cultures and civilizations. It has been used in natural and holistic medicine to treat sore throats, coughs, urinary infections, digestive disorders, skin disorders, arthritis, and to expel tapeworms. However, modern research suggests that it might be useful for the treatment of serious conditions as prostate cancer, skin cancer, osteoarthritis, and diabetes. Studies also show that pomegranate seeds might help clear the digestive system from fats. Clinical research suggested that PG has the potential to thin the blood, increase blood flow to the heart, reduce blood pressure, reduce plaque in the arteries, and reduce bad cholesterol while increasing good one. A decoction of seed is used to treat syphilis while the juice is used to treat jaundice and diarrhea. The flower juice is used to treat nose bleeding. The fruit pulp and the seed are stomachic. Dried, pulverized flower buds are employed as a remedy for bronchitis [10]. Moreover, many studies have shown that PG peel extract has radio- protective, antifibrotic and wound healing properties. In addition, it possesses antioxidant, immunomodulatory, antibacterial, gastroprotectective, larvicidal, antifungal, antitumor, antimicrobial, antiviral and hypoglycemic activities [11, 12]. Also, PG has a protective role against fatty liver in obesity through improvement of abnormal lipid metabolism. On the other hand, the inhibition of carbohydrate digestive enzymes and its phenolic content may contribute to the antihyperglycemic effects of PG flower and peel, and support their claims in diabetes. Other studies indicated that the methanolic extract of PG peel has beneficial influences over the inhibition of induced oxidative stress and histopathological alternations in liver and kidney of female rats, and these effects may be related to antiapoptotic and antioxidant activities [12]. Recent research has focused on the potential effect of PG for the treatment of cardiovascular disease, diabetes, and various forms of cancer [10]. This research was designed to study the effect of streptozotocin (STZ) induced IDDM on food and drink habits, liver function and on International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 7, 2015 Innovare Academic Sciences