Abstract
BackgroundOxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat.MethodsThe DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments.ResultsDegeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction.ConclusionOur results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties.Graphical abstractProtection against neuropathy
Highlights
Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus
Results of two clinical trial studies have shown that fast blood glucose (FBG) and hemoglobin A1c (HbA1c) significantly decreased after consumption of 100 mg Juglans regia L. leaf extract for 3 months [19] and 200 mg Juglans regia L. leaf extract for 2 months [7] compared to placebo groups
We observed a significant increase in lipid peroxidation, a significant reduction of catalyses and superoxide dismutase activity, and a significant reduction of glutathione content in the sciatic nerve
Summary
Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. The seeds, green husks, and leaves of the Persian or common walnut (Juglans regia L.), the best-known member of the Juglans genus, are a rich source of these molecules which have been traditionally used in Iranian folk medicine for treatment of several diseases such as infections, inflammations, and diabetes and its complications [5, 6] These effects were confirmed according to the recent scientific studies [7, 8]. We investigated the beneficial effects and the underlying molecular mechanisms of Juglans regia L. leaf extract in diabetic neuropathy as a common serious complication of diabetes, according to the traditional claims and the existing scientific evidences regarding hypoglycemic and antioxidative properties of Juglans regia L. leaf extract
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