Effect of Berberine Isolated from Barberry Species by Centrifugal Partition Chromatography on Memory and the Expression of Parvalbumin in the Mouse Hippocampus Proper.

Radosław Szalak,Marcin B Arciszewski,Daariimaa Khurelbat,Wirginia Kukula-Koch,Wojciech Koch,Grażyna Biała,Marta Kruk-Słomka,Małgorzata Matysek,Lidia Czernicka

doi:10.3390/ijms22094487

Abstract

Neurodegenerative diseases associated with memory disturbances are important health issues occurring due to a prolonged life span. This article presents the results of a study targeting the emergence of a drug candidate with antiamnesic properties. The effect of berberine (BBR), an isoquinoline alkaloid isolated from the overground parts of Berberis sibirica Pall., on memory and expression of parvalbumin in the mouse hippocampus proper were determined. High-purity BBR was isolated by centrifugal partition chromatography from a methanolic extract from B. sibirica by using a methyl-tert-butyl ether and water (1:1 v/v) solvent system with 10 mmol/L of triethylamine and hydrochloric acid. In an in vivo study, we assessed the influence of the chronic administration of BBR on different stages of memory-related responses in mice. Our results indicated that the chronic administration of BBR in a higher dose (5 mg/kg) improves long-term memory acquisition in mice, as determined in the passive avoidance test. The hippocampal CA1–CA3 fields showed an increased number of parvalbumin-immunoreactive neurons (PV-IR) and nerve fibers as compared to the control. No significant changes in the dentate gyrus were observed between the groups. The HPLC-ESI-QTOF-MS/MS analysis of the biological material revealed the content of BBR as 363.4 ± 15.0 ng (4.11% of RSD) per brain, 15.06 ± 0.89 ng (5.91% of RSD) per hippocampus, and 54.45 ± 1.40 (4.05% of RSD) ng in 100 µL plasma. The study showed that BBR could be a factor influencing the expression of PV in hippocampal neurons. We speculate that BBR may modulate the level of Ca2+ in neurons and thus potentially act as a neuroprotective factor against neuronal damages.

Highlights

IntroductionNeurodegenerative diseases are characterized by the deterioration of cognition that frequently occurs in senile patients
Extract (CPC) was used to isolate BBR from the methanolic extract obtained from the overground parts of B. sibirica and led to the recovery of Centrifugal partition chromatography (CPC) was used to isolate BBR from the methanothe alkaloid with high purity, exceeding 96%—directly from the total extract
An increase of parvalbumin-immunoreactive neurons (PV-IR) neurons after the administration of BBR may suggest the effect of this alkaloid on neuronal Ca2+ metabolism and constitute the basis for further research on the possible neuroprotective role of BBR

Summary

Introduction

Neurodegenerative diseases are characterized by the deterioration of cognition that frequently occurs in senile patients. There is a direct relationship between an increasing life expectancy supported by a better access to medicine and the number of patients suffering from dementia. According to the World Health Organization, the number of people suffering from Alzheimer’s disease (AD) is increasing rapidly. The features of memory impairment occurring during AD progression include memory loss and behavioral changes in patients, cognitive impairment, or even death. These alterations are induced by a disturbed homeostasis of dopaminergic, monoaminergic, and serotoninergic neurotransmission that affects some areas of the brain

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