Chlorogenic acid alleviates the reduction of Akt and Bad phosphorylation and of phospho-Bad and 14-3-3 binding in an animal model of stroke.

Abstract

BACKGROUND:

Stroke is caused by disruption of blood supply and results in permanent disabilities as well as death. Chlorogenic acid is a phenolic compound found in various fruits and coffee and exerts antioxidant, anti-inflammatory, and anti-apoptotic effects.

OBJECTIVES:

The purpose of this study was to investigate whether chlorogenic acid regulates the PI3K-Akt-Bad signaling pathway in middle cerebral artery occlusion (MCAO)-induced damage.

METHODS:

Chlorogenic acid (30 mg/kg) or vehicle was administered peritoneally to adult male rats 2 h after MCAO surgery, and animals were sacrificed 24 h after MCAO surgery. Neurobehavioral tests were performed, and brain tissues were isolated. The cerebral cortex was collected for Western blot and immunoprecipitation analyses.

RESULTS:

MCAO damage caused severe neurobehavioral disorders and chlorogenic acid improved the neurological disorders. Chlorogenic acid alleviated the MCAO-induced histopathological changes and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Furthermore, MCAO-induced damage reduced the expression of phospho-PDK1, phospho-Akt, and phospho-Bad, which was alleviated with administration of chlorogenic acid. The interaction between phospho-Bad and 14-3-3 levels was reduced in MCAO animals, which was attenuated by chlorogenic acid treatment. In addition, chlorogenic acid alleviated the increase of cytochrome c and caspase-3 expression caused by MCAO damage.

CONCLUSIONS:

The results of the present study showed that chlorogenic acid activates phospho-Akt and phospho-Bad and promotes the interaction between phospho-Bad and 14-3-3 during MCAO damage. In conclusion, chlorogenic acid exerts neuroprotective effects by activating the Akt-Bad signaling pathway and maintaining the interaction between phospho-Bad and 14-3-3 in ischemic stroke model.

• Authors: Murad-Ali Shah, Ju-Bin Kang, Myeong-Ok Kim, Phil-Ok Koh
• Journal: Journal of veterinary science (J Vet Sci) Vol. 23 Issue 6 Pg. e84 (Nov 2022) ISSN: 1976-555X [Electronic] Korea (South)
• PMID: 36259103 (Publication Type: Journal Article)
• Copyright: © 2022 The Korean Society of Veterinary Science.

Chemical References

• Bad protein, rat
• bcl-Associated Death Protein
• Chlorogenic Acid
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• 14-3-3 Proteins

Topics

• Animals
• Male
• Rats
• Apoptosis
• bcl-Associated Death Protein (metabolism)
• Brain Ischemia (veterinary)
• Chlorogenic Acid (pharmacology, therapeutic use)
• Disease Models, Animal
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, veterinary)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Sprague-Dawley
• Stroke (drug therapy, veterinary)
• 14-3-3 Proteins (metabolism)