Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice.

Sickness behaviour, a set of behavioural changes associated with neuroinflammation, is expressed as decreased mobility and depressed behaviour. Activation of AMP-activated protein kinase (AMPK) is reported to regulate inflammation in conditions such as Alzheimer and traumatic brain injury. Metformin, an antidiabetic agent acting via AMPK activation, possesses anti-inflammatory properties. Similarly, the reported anti-inflammatory activities of berberine could be partially attributed to its ability to activate AMPK. In this study, we investigated the effects of metformin and berberine against lipopolysaccharide (LPS)-induced sickness-like behaviour, associated with neuroinflammation, impaired cognition, and oxidative stress. Swiss albino mice were divided into four groups, normal control, LPS control, metformin treatment, and berberine treatment. The control groups received saline for 7 days. Groups 3 and 4 received metformin (200 mg/kg) and berberine (100 mg/kg), respectively, orally once daily for 7 days. On day 7, 1 h after the treatments, animals received LPS (1.5 mg/kg i.p.) to induce sickness-like behaviour. Open field test (OFT) and forced swim test (FST), were performed within 2 h of LPS administration. Then, proinflammatory cytokines (IL-1