Protective effect of furelic acid on lipopolysaccharide induced damage in PC12 cells and hippocampal neurons of rats / 中国药理学与毒理学杂志

ABSTRACT

OBJCTIVE To investigate the protective effect of ferulic acid (FA) on lipopolysaccharide (LPS)-induced damage to PC12 cells and hippocampal neurons in Sprague-Dawley (SD) rats and its potential mechanisms. METHODS ① in vitro studyPC12 cells were pretreated with FA 2.5-40 μmol · L-1 for 12 h and treated with LPS for another 8 h. CCK-8 kit was used to test PC12 cell viability. Inflammatory cytokines tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were de?tected by ELISA kits. Laser scanning confocal microscopy was performed to measure F-actin expres?sion in the cells. ②in vivo studyFA 25,50 and 100 mg · kg-1 was ip given to Sprague-Dawley(SD) rats once a day for 35 d,and from the 29th day,ip co-administered with LPS(0.2 mg · kg-1)for 7 d. Immunohistochemistry method was used to determine protein expression of phophodiestera 4B (PDE4B)in the hippocampus of rats. The protein expression of cAMP response element-binding protein (CREB) and phospho CREB (p-CREB) was determined by Western blotting. RESULTS In the in vitro study,compared with LPS group,cell viability was significantly increased in FA 10,20 and 40μmol·L-1 groups(P<0.05),while the production of inflammatory cytokines TNF-α and IL-1β decreased(P<0.05). The structure and distribution of cytoskeletal protein F-actin were ameliorated markedly in PC12 cells. In the in vivo study,hematoxylin-eosin(HE)staining showed that pretreatment with FA(50 and 100 mg·kg-1) alleviated the damage to the hippocampus induced by LPS in SD rats. Immunohistochemistry showed that FA(50 and 100 mg·kg-1)pretreatment effectively prevented LPS-induced up-regulation of PDE4B expression in the hippocampus of rats(P<0.05). Western blotting analysis showed that the inhibitory effects on the protein expressions of CREB and p-CREB induced by LPS were altered by FA(50 and 100 mg · kg-1)pretreatment(P<0.05). CONCLUSION FA can protect against LPS induced damage to PC12 cells and hippocampal neurons of rats. The resistant effect on neuron-inflammation of FA may be conferred by inhibiting LPS-induced up-regulation of PDE4B and stimulating signaling pathways of cAMP/CREB.