Effects of epigallocatechin-3-gallate on systemic inflammation-induced cognitive dysfunction in aged rats

Abstract

In this study, we examined the effects of epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on sepsis-induced neurocognitive abnormity in aged rats. Aged rats received an intraperitoneal (i.p.) injection of 5.0mg/kg lipopolysaccharide (LPS) or saline. Animals were further divided into three groups: control, low-dose EGCG (4.0mg/kg), and high-dose EGCG (20mg/kg). EGCG was i.p. injected at the same time, 24 and 48h after LPS administration. Survival rate was recorded for 1week. All surviving animals were assessed for cognitive function using the novel object recognition test, followed by measurement of hippocampal cytokine levels. In an additional set of experiments, the liver function test was performed. Furthermore, the effects of EGCG on cytokine release from microglia isolated from young and aged rats were assessed. The survival rate in LPS-treated control rats was 77.8%, which was decreased to 72.2 and 33.3% in the low and high EGCG groups, respectively. In the surviving animals, the LPS-treated control rats exhibited impaired cognitive performance and increased pro-inflammatory cytokine levels compared with untreated animals. None of these neurocognitive alterations were affected by low or high EGCG treatment. Blood chemical analysis showed co-administration of EGCG with LPS resulted in a marked increase in both aspartate aminotransferase and alanine aminotransferase levels. In addition, EGCG inhibited LPS-induced cytokine release, whereas the suppressive ability of EGCG was lower in aged microglia compared with in young microglia. Our findings demonstrated that EGCG cannot prevent hippocampal neuroinflammation and related memory deficits in aged rats surviving sepsis.