Effect of protocatechuic acid on cognitive processes and central nervous system neuromodulators in the hippocampus, prefrontal cortex, and striatum of healthy rats

ABSTRACT

Objective

: This study aimed to investigate the influence of protocatechuic acid (PCA) on learning, memory, and central nervous system (CNS) neuromodulators in healthy rats, to analyse whether the procognitive effects of PCA found in animal models of memory impairment and described in the literature occur in healthy individuals.

Methods

: PCA was administered p.o. for 48 days at doses of 50 or 100 mg/kg body weight. The cognitive performance was analysed in behavioural tests (open field, novel object recognition, water maze). Then the animals were sacrificed and their hippocampi, prefrontal cortices and striata removed to measure the level of serotonin, dopamine (DA), noradrenaline, their metabolites and amino acids (taurine, histidine, serine, glutamic acid, aspartic acid, γ-aminobutyric acid, alanine) using high-performance liquid chromatography.

Results

: No obvious behavioural changes were observed. Post-mortem quantification of monoamines showed that the turnover of DA in the striatum was significantly increased by PCA. Moreover, hippocampal, and cortical levels of histidine were influenced by PCA and significantly decreased.

Conclusion

: Despite many beneficial effects of PCA in experimentally developed cognitive impairments, it has no sharp effect on memory performance in healthy rats. The influence on the turnover of striatal DA and modulation of the amino acid system by affecting the concentration of histidine deserves a deeper examination due to the role of histamine in neuropsychiatric disorders as well as the functional interactions between histidine and DA metabolism in the brain.

KEYWORDS:

• Protocatechuic acid
• memory
• learning
• brain
• neurotransmitter
• rat

Acknowledgements

The authors would like to thank Ewa Wojnar, MSc and Patrycja Kozlowska, MSc for their assistance in sample preparation and chromatographic analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Ministry of Science and Higher Education [grant number 1M9/PM2/18].

Notes on contributors

Kinga Krzysztoforska

Kinga Krzysztoforska is a PhD candidate in the Department of Experimental and Clinical Pharmacology at the Medical University of Warsaw. She graduated from the Medical University of Lublin with a master’s degree in pharmacy and completed postgraduate specialisation studies in clinical pharmacy. She works in Children’s Memorial Health Institute in hospital pharmacy. Her research interests focus on neurodegenerative diseases and the influence of various substances on memory processes.

Agnieszka Piechal

Agnieszka Piechal obtained the title of medical doctor at the Medical University in Warsaw. Already during her studies and up to the present time, she is associated with the Department of Experimental and Clinical Pharmacology. Moreover, she also works as a neurologist at the Institute of Psychiatry and Neurology. She is also a specialist in clinical pharmacology. Her interests focus on studying the effects of preparations of plant origin and synthetic compounds on cognitive processes and animal behaviour.

Kamilla Blecharz-Klin

Kamilla Blecharz-Klin is an assistant professor in the Department of Experimental and Clinical Pharmacology at the Medical University of Warsaw. Her main areas of interest are the neuropharmacology, neurotoxicology and mechanisms responsible for cognitive processes. She published research concerned the impact of well-known and tested pharmacological agents on the central nervous system and behaviour in various experimental models.

Justyna Pyrzanowska

Justyna Pyrzanowska MD, PhD works in the Department of Experimental and Clinical Pharmacology at the Medical University of Warsaw. She graduated from the Medical University of Warsaw and next obtained a PhD in Pharmacology. She specialised in Family Medicine. Her main research area is experimental pharmacology with a focus on phytotherapy and neurocognitive disorders.

Ilona Joniec-Maciejak

Ilona Joniec-Maciejak is an employee of the Department of Experimental and Clinical Pharmacology at the Medical University of Warsaw. She received her Ph.D. degree in 2007; in 2019, she received her postdoctoral degree. Her research interests focus on mechanisms of neurodegeneration. She is also involved in the search of neuroprotective compounds.

Dagmara Mirowska-Guzel

Dagmara Mirowska-Guzel is clinical pharmacologist and neurologist. She is a head of Chair and Department of Experimental and Clinical Pharmacology Medical University of Warsaw and works as neurologist in outpatient clinic in Institute of Psychiatry and Neurology in Warsaw. She conducted some of her research in cooperation with Max-Planck-Institute for Psychiatry in Munich. She is a chair of The Committee on Therapeutics and Pharmaceutical Sciences of the Polish Academy of Sciences. Her area of interest includes clinical pharmacology, demyelinating and neurodegenerative diseases.

Ewa Widy-Tyszkiewicz

Ewa Widy-Tyszkiewicz is a pharmacologist in the Department of Experimental and Clinical Pharmacology Medical University of Warsaw, Poland. She studied medicine in Warsaw and conducted her research at Department of Neurochemistry of McGill University, Montreal, Canada, and Institute of Biological Psychiatry Sct. Hans Hospital, Roskilde, Denmark. She is a Member of EMA HMPC Working Party on Community Monographs and Community List. Her areas of research include pharmacology, toxicology, cognitive neuroscience, and herbal medicines.