Neuroprotective effect of emodin on acute brain injury in sepsis mice

Objective To investigate the neuroprotective effect and corresponding mechanism of emodin on acute brain injury in sepsis mice. Methods Male BALB/c mice were randomly divided into four groups: normal control group, lipopolysaccharide (LPS) group, emodin group and emodin+LPS group. Mice in emodin group and emodin+LPS group were administered with emodin (20mg/kg) 30min before modeling, and in the other two groups were with same volume solvent. Then the mice in LPS group and emodin+LPS group were stimulated with LPS (15mg/kg), and in the other two groups, meanwhile, received the same volume of normal saline. Mice were sacrificed 18h after LPS injection, and brain tissues and plasma samples were collected. Hematoxylin-eosin staining was performed to observe the pathological changes of brain tissues; the expression of S100-β protein in plasma was measured by ELISA to evaluate the degree of brain injury; the production of lactic acid (LA) in brain tissue was detected by colorimetric quantitative method to evaluate the degree of metabolic disorder in brain tissue; the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in plasma were measured by ELISA to evaluate the degree of systemic inflammatory response; the activity of neuro-specific enolase (NSE) was measured by ELISA to evaluate the degree of neuroinflammation; the activity of acetylcholinesterase (Ach-E) in brain tissue was measured by colorimetric quantitative method to evaluate the level of acetylcholine (Ach) in brain tissue. Results Compared with normal control group, no obvious pathological damage of brain tissues was observed in emodin group, but obvious pathomorphological brain injury was observed in LPS group; While compared with LPS group, a significantly lighter degree of brain injury was found in emodin+LPS group; The levels of Ach-E and LA in brain tissue in LPS group [(1.09±0.10)U/mg and (0.35±0.03)mmol/g, respectively] markedly increased in comparison with those in normal control group [(0.84±0.09)U/mg and (0.16±0.03)mmol/g, respectively, P<0.05]; The plasma levels of S100β, IL-6, TNF-α and NSE in LPS group [(0.52±0.06)ng/ml, (4207.23±90.76)pg/ml, (355.62±6.88)pg/ml and (9.02±0.78)ng/ml, respectively] were also significantly higher than those in normal control group [(0.38±0.05)ng/ml, (501.60±74.18)pg/ml, (157.41±10.65) pg/ml and (5.41±0.89)ng/ml, respectively, P<0.05]; No statistically significant differences were observed in these indexes between emodin group and normal control group (P>0.05); Compared with LPS group, the plasma levels of S100β [(0.44±0.06) ng/ml], IL-6 [(1479.50±50.53)pg/ml], TNF-α [(213.48±9.19)pg/ml] and NSE [(6.74±1.12)ng/ml] in emodin+LPS group significantly reduced (P<0.05), and the levels in brain tissue of LA [(0.25±0.03)mmol/g protein] and Ach-E [(0.87±0.07)U/mg protein] also markedly down-regulated in emodin+LPS group (P<0.05). Conclusion Emodin may have a protective effect on LPS-induced acute brain injury in mice, the mechanism is possibly activation of cholinergic anti-inflammatory pathway and inhibition of inflammatory response.