Can Magnoflorine Improve Memory? Immunohistochemical Studies on Parvalbumin Immunoreactive Neurons and Fibers of Mice Hippocampus

<b>Background/Objectives</b>: We assessed the influence of long-term injection of magnoflorine (MAG) on memory acquisition in mice for the first time. <b>Methods</b>: This isoquinoline alkaloid that belongs to the aporphines was isolated from the roots of <i>Berberis vulgaris</i> by centrifugal partition chromatography (CPC) using a biphasic solvent system composed of chloroform: methanol: water in the ratio 4:3:3 (<i>v</i>/<i>v</i>/<i>v</i>) with 20 mM of hydrochloric acid and triethylamine, within 64 min. <b>Results</b>: Our results indicated that long-term injection of MAG 20 mg/kg dose improve the long-term memory acquisition in mice that were evaluated in the passive avoidance (PA) test with no toxicity records. The analysis of brain lysates and animal plasma by HPLC-ESI-QTOF-MS/MS showed the ability of the compound to cross the blood-brain barrier, and an elevated level of phosphatidylcholine PC (14:1(9Z)/14:1(9Z)) with the molecular formula of C₃₆H₆₉NO₈P was observed in both treated groups with 10 mg/kg and 20 mg/kg MAG in comparison to the control group. <b>Conclusions</b>: This phenomenon may explain MAG's cognition-enhancing properties as the PC may induce the synthesis and strengthening of neuronal cells. Also, the 7-day-long administration of MAG at 10 mg/kg and 20 mg/kg increased the mean number of parvalbumin (PV)-IR neurons in the hippocampus. Statistically, the largest PV-IR neurons were observed at the 20 mg/kg dose, which may indicate a potential effect of MAG on Ca²⁺ metabolism. However, no statistical differences were observed in the mean number of PV-IR nerve fibers in both doses of MAG, regardless of the hippocampal fields. This positive effect of MAG on hippocampal neurons provides further support for the neuroprotective effect of this alkaloid.