Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, India.
School of Pharmacy and Pharmacology, MHIQ, QUM Network, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
Inflammopharmacology. 2019 Oct;27(5):941-948. doi: 10.1007/s10787-019-00638-w. Epub 2019 Sep 3.
Metformin (MET), a biguanide oral hypoglycaemic agent, recently has been shown to be effective in various conditions other than type-2 diabetes including cancer, stroke, weight reduction, and polycystic ovarian syndrome, to name a few. MET has also possessed antioxidant and antiinflammatory properties by activation of AMPK . This study was aimed at evaluating the effects of MET on lipopolysaccharide (LPS)-induced systemic and neuroinflammation, oxidative stress, and behavioural changes. The study consisted of six groups, where three selected doses of MET (100, 200, and 300 mg/kg) were employed in male Swiss albino mice, with one group of imipramine (IMI), saline, and LPS each. Systemic inflammation was induced by injecting LPS (1.5 mg/kg) by intraperitoneal route. A battery of behavioural tests including open field, forced swim, and tail suspension tests were employed to assess the impact of systemic inflammation on exploratory behaviour and learned helplessness. LPS induced significant immobility with profound symptoms of sickness behaviour. Furthermore, LPS led to significant increase in serum and brain proinflammatory cytokines TNF-α and IL-6; and also increased lipid peroxidation with reduced glutathione levels. Pretreatment of the animals with 100 and 200 mg/kg of MET significantly reduced both systemic and central inflammatory markers along with protecting against LPS-induced oxidative stress. The higher dose, 300 mg/kg of MET was not effective against most of LPS-induced biochemical changes. Our preliminary results from this study suggest the antiinflammatory and neuroprotective effects of MET in LPS-induced model of sickness behaviour and neuroinflammation.
二甲双胍（MET）是一种双胍类口服降糖药，最近已被证明在除 2 型糖尿病以外的多种疾病中有效，包括癌症、中风、减肥和多囊卵巢综合征等。MET 通过激活 AMPK 还具有抗氧化和抗炎特性。本研究旨在评估 MET 对脂多糖（LPS）诱导的全身和神经炎症、氧化应激和行为变化的影响。该研究包括六个组，其中三种选定剂量的 MET（100、200 和 300mg/kg）用于雄性瑞士白化小鼠，一组使用丙咪嗪（IMI）、生理盐水和 LPS。通过腹腔内途径注射 LPS（1.5mg/kg）诱导全身炎症。一系列行为测试，包括旷场、强迫游泳和悬尾测试，用于评估全身炎症对探索性行为和习得性无助的影响。LPS 诱导明显的不动性，并伴有严重的疾病行为症状。此外，LPS 导致血清和大脑促炎细胞因子 TNF-α 和 IL-6 显著增加；并降低谷胱甘肽水平导致脂质过氧化增加。用 100 和 200mg/kg 的 MET 预处理动物可显著降低全身和中枢炎症标志物，同时防止 LPS 诱导的氧化应激。较高剂量（300mg/kg）的 MET 对 LPS 诱导的大多数生化变化无效。我们从这项研究中得出的初步结果表明，MET 具有抗 LPS 诱导的疾病行为和神经炎症的抗炎和神经保护作用。
