Shivavedi Naveen, Kumar Mukesh, Tej Gullanki Naga Venkata Charan, Nayak Prasanta Kumar
Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India.
Brain Res. 2017 Nov 1;1674:1-9. doi: 10.1016/j.brainres.2017.08.019. Epub 2017 Aug 18.
Diabetes mellitus and depression are the common comorbid disorders affecting humans worldwide. There is an unmet need to develop therapeutic strategies to treat both diabetes mellitus and comorbid depression. The present study evaluated the effectiveness of metformin and ascorbic acid against type 2 diabetes mellitus and comorbid depression in rats. Four groups of diabetic rats were orally administered with vehicle (1mL/kg), metformin (25mg/kg), ascorbic acid (25mg/kg), or combination of metformin (25mg/kg) and ascorbic acid (25mg/kg) for 11 consecutive days. Diabetes was induced by single-dose administration of streptozotocin (65mg/kg, i.p.) with nicotinamide (120mg/kg, i.p.). Comorbid depression was induced by five inescapable foot-shocks (2mA, 2ms duration) at 10s intervals on days 1, 5, 7, and 10. One group of healthy rats received only vehicles to serve as nondiabetic control group. On day 11, animals were sacrificed, and blood and brain samples were collected from each rat following forced swim test. Plasma glucose, insulin, and corticosterone levels were estimated in plasma. The levels of monoamines, proinflammatory cytokines, and oxidative stress were measured in prefrontal cortex. The combination therapy significantly reduced immobility period, glucose, and corticosterone levels relative to diabetes with comorbid depression group. Furthermore, the combination therapy increased the levels of insulin and monoamines, and caused a significant reductions in oxidative stress and proinflammatory cytokines. In conclusion, the present study revealed that metformin and ascorbic acid combination therapy could be a potential strategy to treat type 2 diabetes mellitus and comorbid depression.
糖尿病和抑郁症是影响全球人类的常见共病。开发同时治疗糖尿病和共病抑郁症的治疗策略仍存在未满足的需求。本研究评估了二甲双胍和抗坏血酸对大鼠2型糖尿病和共病抑郁症的疗效。将四组糖尿病大鼠连续11天口服给予赋形剂（1mL/kg）、二甲双胍（25mg/kg）、抗坏血酸（25mg/kg）或二甲双胍（25mg/kg）与抗坏血酸（25mg/kg）的组合。通过腹腔注射单剂量链脲佐菌素（65mg/kg）和烟酰胺（120mg/kg）诱导糖尿病。在第1、5、7和10天，通过每隔10秒给予五次不可逃避的足部电击（2mA，持续2ms）诱导共病抑郁症。一组健康大鼠仅接受赋形剂作为非糖尿病对照组。在第11天，处死动物，并在强迫游泳试验后从每只大鼠收集血液和脑样本。测定血浆中的血糖、胰岛素和皮质酮水平。在前额叶皮质中测量单胺、促炎细胞因子和氧化应激水平。与糖尿病合并抑郁症组相比，联合治疗显著缩短了不动时间、降低了血糖和皮质酮水平。此外，联合治疗提高了胰岛素和单胺水平，并显著降低了氧化应激和促炎细胞因子水平。总之，本研究表明二甲双胍和抗坏血酸联合治疗可能是治疗2型糖尿病和共病抑郁症的潜在策略。
