Abstract
Purpose: To investigate the protective effect of morin, a naturally occurring bioflavonoid of Moraceae family, in experimentally-induced diabetic neuropathy (DN) in rats.Methods: Diabetes was induced by a single injection (65 mg/kg, ip) of streptozotocin (STZ). Morin (15 and 30 mg/kg/day) oral treatment was started 3 weeks after diabetes induction and continued for 5 consecutive weeks. Pain threshold behavior tests were performed at the end of the treatment. In sciatic nerve, inflammatory cytokines (TNF-á, IL-1â, IL-6), nerve growth factor (NGF) and insulin growth factor (IGF-1) were determined using ELISA kits, while thiobarbituric acid reactive substances (TBARS),glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were assessed.Results: Diabetic animals showed apparent decreased paw-withdrawal (39 %, p < 0.05) and tail-flick (31 %, p < 0.05) latency as compared with control group. All the measured biomarkers were altered (p < 0.05 to 0.001) in diabetic rats compared with control non-diabetic animals. Morin treatment attenuated hyperalgesia and analgesia (p < 0.05) respectively. Morin treatment of diabetic rats at both doses significantly decreased the levels of cytokines (p < 0.01), glucose (p < 0.01) and TBARS (p < 0.001), but increased NGF (p < 0.01), IGF-1 (p < 0.01) and GSH (p < 0.01) levels in sciatic nerves compared to untreated diabetic animals. Inhibited activities (U/mg protein) of SOD (1.08 ± 0.16) and CAT (2.77 ± 0.36) in sciatic nerve of diabetic rats also found corrections (2.09 ± 0.11, p < 0.01) and (4.53 ± 0.57, p < 0.01) after morin (30 mg/kg/day) treatment, compared with untreated diabetic animals.Conclusion: These findings demonstrate the protective effect of morin mediated through reduction of oxidative stress and inflammatory process, and suggest the therapeutic potential of morin in the attenuation of diabetic neuropathy.Keywords: Morin, Diabetes, Neuropathy pain, Oxidative stress, Anti-inflammatory
Highlights
Neuropathic pain is a form of chronic pain induced by damage or abnormal function of central or peripheral nervous system [1] and it associated with diabetes metabolic syndromes
Fasting glucose levels markedly (p < 0.001) increased while the insulin values decreased in STZ-induced diabetic rats compared to controls
The results obtained from the present study reveal that morin ameliorates hyperglycemiainduced mechanical or thermal hyperalgesia and lowers neuropathic pain by reducing oxidative stress in the nerve of diabetic rats by virtue of its antioxidative and anti-inflammatory properties
Summary
Neuropathic pain is a form of chronic pain induced by damage or abnormal function of central or peripheral nervous system [1] and it associated with diabetes metabolic syndromes. Male Wistar albino rats, approximately 3 months old, weighing 260 – 285 g were received from Experimental Animal Care Center (King Saud University, Riyadh, Saudi Arabia). They were maintained under controlled conditions of temperature (22 ± 1 oC), humidity (50-55 %), and light (12 h light/dark cycles) and were provided with Purina chow (Manufactured by Grain Silos & Flour Mills Organization, Riyadh, Saudi Arabia) and drinking water ad libitum. With the aid of nitroblue tetrazolium as the indicator, SOD activity in sciatic nerve was estimated in the post-mitochondrial supernatant according to the method described by Kono [22]. All statistics tests were conducted using Graph Pad Prism (version 5) software
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