Effects of sodium ferulate on amyloid‐beta‐induced MKK3/MKK6‐p38 MAPK‐Hsp27 signal pathway and apoptosis in rat hippocampus

Aim : To observe the effects of sodium ferulate (SF) on amyloid beta (Aβ) 1–40 induced p38 mitogen‐activated protein kinase (MAPK) signal transduction pathway and the neuroprotective effects of SF. Methods : Rats were injected intracerebroventricularly with Aβ 1–40 . Six hours after injection, Western blotting was used to determine the expressions of phosphorylated mitogen‐activated protein kinase kinase (MKK) 3/MKK6, phospho‐p38 MAPK, interleukin (IL)‐1β, phospho‐MAPK activating protein kinase 2 (MAPKAPK‐2), the 27 kDa heat shock protein (Hsp27), procaspase‐9, ‐3, and ‐7 cleavage, and poly (ADP‐ribose) polymerase (PARP) cleavage. Seven days after injection, Nissl staining was used to observe the morphological change in hippocampal CA1 regions. Results : Intracerebroventricular injection of Aβ 1–40 induced an increase in phosphorylated MKK3/MKK6 and p38 MAPK expressions in hippocampal tissue. These increases, in combination with enhanced interleukin (IL)‐1β protein expression and reduced phospho‐MAPKAPK2 and phospho‐Hsp27 expression, mediate the Aβ‐induced activation of cell death events as assessed by cleavage of procaspase‐9, ‐3, and ‐7 and caspase‐3 substrate PARP cleavage. Pretreatment with SF (100 mg/kg and 200 mg/kg daily, 3 weeks) significantly prevented Aβ 1–40 ‐induced increases in phosphorylated MKK3/MKK6 and p38 MAPK expression. The Aβ 1–40 ‐induced increase in IL‐1β protein level was attenuated by pretreatment with SF. In addition, Aβ 1–40 ‐induced decreases in phosphorylated MAPKAPK2 and Hsp27 expression were abrogated by administration of SF. In parallel with these findings, Aβ 1–40 ‐induced changes in activation of caspase‐9, caspase‐7, and caspase‐3 were inhibited by pretreatment with SF. Conclusion : SF prevents Aβ 1–40 ‐induced neurotoxicity through suppression of MKK3/MKK6‐p38 MAPK activity and IL‐1β expression and upregulation of phospho‐Hsp27 expression.