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Abstract Title:

Ferulic Acid Exerts Anti-apoptotic Effects against Ischemic Injury by Activating HSP70/Bcl-2- and HSP70/Autophagy-Mediated Signaling after Permanent Focal Cerebral Ischemia in Rats.

Abstract Source:

Am J Chin Med. 2019 ;47(1):39-61. Epub 2019 Jan 7. PMID: 30612456

Abstract Author(s):

Chin-Yi Cheng, Shung-Te Kao, Yu-Chen Lee

Article Affiliation:

Chin-Yi Cheng

Abstract:

This study assessed the anti-apoptotic effects of the administration of ferulic acid (FrA) in rats 30min before middle cerebral artery occlusion (MCAo) followed by 3 d of ischemia and the involvement of 70kDa heat shock protein (HSP70)-mediated signaling in the penumbral cortex. Our results demonstrated that FrA pretreatment at doses of 80mg/kg (FrA-80mg) and 100mg/kg (FrA-100mg) effectively ameliorated neurological functions and reduced the numbers of cytochrome c-, cleaved caspase-3-, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in the penumbral cortex 3 d after ischemia. Moreover, FrA-80mg and FrA-100mg pretreatment markedly upregulated cytosolic HSP70, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) A/B-II and autophagy-related protein 5 (Atg5) expression; cytosolic and mitochondrial X-linked inhibitor of apoptosis (XIAP) expression and the Bcl-2/Bax ratio. FrA pretreatment downregulated cytosolic cytochrome c, apoptosis-inducing factor (AIF), procathepsin B, and cathepsin B expression and mitochondrial and cytosolic second mitochondria-derived activator of caspase/direct inhibitor of apoptosis protein-binding protein with a low isoelectric point (Smac/DIABLO) expression in the penumbral cortex. Pretreatment with VER155008, a HSP70 family inhibitor, significantly inhibited the effects of FrA-100mg on the expression of the aforementioned proteins expression in the penumbral cortex. FrA-80mg and FrA-100mg pretreatment exerts neuroprotective effects against caspase-dependent and -independent apoptosis through activating HSP70/Bcl-2- and HSP70/autophagy-induced signaling pathways. Furthermore, the HSP70/Bcl-2- and HSP70/autophagy-induced anti-apoptotic effects of FrA pretreatment can be attributed to the regulation of Bax/cytochrome c/Smac/DIABLO/XIAP/ caspase-3- (or Bax/AIF-) and Beclin-1/LC3A/B-II/Atg5-mediated signaling, respectively, in the penumbral cortex 3 d after permanent MCAo.

Study Type : Animal Study

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