Stabilization of mitochondrial function by chlorogenic acid protects against kainic acid-induced seizures and neuronal cell death in rats

• Published in: European journal of pharmacology Vol. 961; p. 176197
• Main Authors: Pai, Ming-Shang, Wang, Kaw-Chen, Yeh, Kun-Chieh, Wang, Su-Jane
• Format: Journal Article
• Language: English
• Published: Netherlands 15-12-2023
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Cell Death; Chlorogenic Acid - pharmacology; Chlorogenic Acid - therapeutic use; Glutamates - pharmacology; Kainic Acid - toxicity; Mitochondria; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Rats; Seizures - chemically induced; Seizures - metabolism; Seizures - prevention & control; Ubiquitin-Protein Ligases - metabolism; Chlorogenic acid; Mitochondrial homeostasis; Kainic acid; Hippocampus; Antiseizure
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2023.176197

The current study investigated the effect of chlorogenic acid, a polyphenolic compound found in numerous plant products, on a kainic acid-induced seizure rat model and its potential mechanism. Rats were administered chlorogenic acid (10 and 50 mg/kg) intraperitoneally for 30 min before kainic acid (15 mg/kg) intraperitoneal administration. Pretreatment with chlorogenic acid decreased the seizure score, increased the latency to onset of the first seizure, and decreased the mortality rate. Chlorogenic acid pretreatment also resulted in a significant reduction in glutamate elevation and neuronal death in the hippocampus of kainic acid-treated rats. In addition, electron microscopy revealed that kainic acid-induced changes in hippocampal mitochondrial structure were prevented by chlorogenic acid pretreatment. Additionally, the levels of mitochondrial function-related proteins, including sirtuin 3, Complex I, glutamate dehydrogenase 1 and ATP synthase, were increased, and the level of the mitochondrial damage marker cytochrome C was decreased in the hippocampus of chlorogenic acid/kainic acid rats. Furthermore, the expression of mitochondrial biogenesis-related proteins [AMP-activated protein kinase (AMPK), sirtuin1, and peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α)] and mitophagy-related proteins [phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), Parkin, and microtubule-associated protein 1 light chain 3 (LC3)] was decreased in the hippocampus of kainic acid-treated rats, which was reversed by chlorogenic acid pretreatment. These observations reveal the marked neuroprotective potential of chlorogenic acid against kainic acid-induced neurotoxicity and seizures through prevention of glutamate increase and preservation of AMPK/sirtuin 1/PGC-1α-mediated mitochondrial biogenesis and PINK1/Parkin-induced mitophagy to maintain adequate mitochondrial homeostasis and function.