Neuroprotective Effect of the Combined Extract of Mentha piperita and Cornus officinalis Against Neuronal Cell Death and Scopolamine-Induced Memory Impairment

TL;DR

A combination of Mentha piperita and Cornus officinalis extracts protects neurons and improves memory in rats, suggesting potential for treating cognitive decline.

Contribution

The study demonstrates the neuroprotective and memory-enhancing effects of a combined Mentha piperita and Cornus officinalis extract in both cell and animal models.

Findings

The MC extract reduced H2O2-induced cell injury and increased BDNF mRNA in SK-N-SH cells.

MC improved cognitive performance in scopolamine-induced memory-impaired rats, as shown by behavioral tests.

MC restored hippocampal acetylcholine levels and upregulated BDNF and related signaling pathways.

Abstract

Mild cognitive impairment (MCI) represents an intermediate stage between normal aging and Alzheimer’s disease. This study investigated the neuroprotective effects of a combined extract of Mentha piperita (MP) and Cornus officinalis (CO) (MC) using in vitro and in vivo models. In SK-N-SH cells, pretreatment with MC (50–150 μg/mL) significantly attenuated H2O2-induced cellular injury, as evidenced by a reduction in Annexin V-positive cells and an increase in brain-derived neurotrophic factor (BDNF) mRNA expression. Rosmarinic acid and loganin, the marker compounds of MP and CO, alone or combined at a 6:4 ratio, mitigated H2O2-induced decreases in cell viability and BDNF mRNA. In the in vivo study, male Sprague–Dawley rats were orally administered MC (50, 100, or 200 mg/kg/day) for 28 days, with phosphatidylserine (50 mg/kg/day) serving as a positive control. MC administration significantly improved cognitive performance in rats with scopolamine-induced memory impairment, as demonstrated by increased step-through latency in the passive avoidance test and reduced escape latency in the Morris water maze. Furthermore, in the probe trial, MC-treated rats spent significantly more time in the target quadrant, indicating enhanced spatial memory retention. Mechanistically, MC restored hippocampal acetylcholine levels and reversed the scopolamine-induced decrease in BDNF and its downstream signaling. Specifically, MC upregulated hippocampal BDNF expression and enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and cAMP response element-binding protein (CREB). In conclusion, these results demonstrate that the MC extract possesses potent neuroprotective and learning- and memory-enhancing effects, highlighting its potential as a therapeutic candidate for managing age-related cognitive decline and MCI.

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