Anti-Neuroinflammation Effect of Standardized Ethanol Extract of Leaves of Perilla frutescens var. acuta on Aβ-Induced Alzheimer’s Disease-like Mouse Model

<b>Background/Objectives:</b><i>Perilla frutescens</i> var. <i>acuta</i> Kudo, a member of the Lamiaceae family, has been previously reported to reduce neuroinflammation and potentially decrease Aβ plaque accumulation in 5XFAD mice. In this study, we aimed to evaluate the anti-neuroinflammatory potential of a standardized 60% ethanol extract of Perilla leaves (PE), optimized for commercial application. <b>Methods</b>: The inflammatory response was assessed in LPS-stimulated BV2 microglial cells, and the cognitive improvement was evaluated in an AD animal model induced by intracerebroventricular injection of Aβ. <b>Results</b>: Using LPS-stimulated BV2 microglial cells and an Aβ-injected ICR mouse model of Alzheimer's disease, we found that PE significantly suppressed the LPS-induced production of nitric oxide and pro-inflammatory mediators, including IL-6, TNF-α, NF-κB, iNOS, and COX-2, along with inhibition of JNK and p38 MAPK activation. Furthermore, PE upregulated CREB and BDNF expression. In vivo, PE administration alleviated Aβ-induced cognitive deficits, which were associated with reduced expression of JNK, NF-κB, iNOS, and COX and increased CREB/BDNF signaling in the hippocampus. Behavioral assessments-including passive avoidance, Morris water maze, novel object recognition, and Y-maze tests-confirmed the improvement in cognitive function. <b>Conclusions</b>: Collectively, these findings demonstrate that PE exerts significant anti-neuroinflammatory and neuroprotective effects, supporting its potential as a functional ingredient for cognitive enhancement.