Protective effects of nigranoic acid on cerebral ischemia-reperfusion injury and its mechanism involving apoptotic signaling pathway.

Abstract

The goal of this study was to assess the expression of poly ADP-ribose polymerase (PARP) and apoptosis-inducing factor (AIF) in the hippocampal CA1 region, and to find out whether nigranoic acid treatment exhibits protective effects on brain through PARP/AIF signaling pathway in cerebral ischemia-reperfusion animal model. Rats were randomly divided into three groups: Sham-surgery, ischemia-reperfusion, and nigranoic acid-treated. Rat models of middle cerebral artery occlusion were prepared using a way of thread occlusion. Rats in the nigranoic acid group were administered with 1 mg/kg intragastric nigranoic acid 6 and 2 h before brain ischemia, respectively. Following reperfusion, samples were collected at different time-points (6, 24, and 72 h) and each group was further divided into three subgroups. Apoptosis was measured using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling method. The protein expression levels of AIF and PARP were detected using Western blot and AIF mRNA quantity was evaluated using the reverse transcription-polymerase chain reaction. Apoptosis, levels of AIF and PARP protein expression, and levels of AIF mRNA expression were significantly increased in the ischemia-reperfusion group compared with the sham-surgery group. However, apoptosis and the expression levels of AIF protein, PARP protein, and AIF mRNA at different time-points were significantly decreased in the nigranoic acid-treated group compared with the model group. We can judge that nigranoic acid has a strong protective effect on rat cerebral ischemia-reperfusion injury, and acts by downregulating nerve cell apoptosis by preventing the overactivation of PARP and AIF nuclear translocation.

• Authors: Tianda Feng, Yunhui Liu, Chao Li, Zhen Li
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 71 Issue 1 Pg. 345-51 (Jan 2015) ISSN: 1559-0283 [Electronic] United States
• PMID: 25168103 (Publication Type: Journal Article)

Chemical References

• Apoptosis Inducing Factor
• RNA, Messenger
• Triterpenes
• nigranoic acid
• Poly(ADP-ribose) Polymerases

Topics

• Active Transport, Cell Nucleus (drug effects)
• Animals
• Apoptosis (drug effects)
• Apoptosis Inducing Factor (genetics, metabolism)
• Brain Ischemia (complications)
• CA1 Region, Hippocampal (drug effects, metabolism, pathology)
• Cell Nucleus (drug effects, metabolism)
• Cytoprotection (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Neurons (drug effects, pathology)
• Poly(ADP-ribose) Polymerases (metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications, metabolism, pathology, prevention & control)
• Signal Transduction (drug effects)
• Triterpenes (pharmacology)