Cognitive-Enhancing and Neuroprotective Effects of a Combination Extract of Atractylodes macrocephala and Rumex acetosa Against Scopolamine-Induced Memory Impairment

This study investigated the cognitive-enhancing and neuroprotective effects of a mixed extract of Atractylodes macrocephala Koidzumi (AM) and Rumex acetosa L. (RA) in models of scopolamine (SCO)-induced toxicity and memory impairment. In vitro, the 2:1 ratio maximized neuroprotection and p-CREB/CREB expression in SCO-treated SH-SY5Y cells. In vivo, rats received the AR mixture orally for 29 days, with SCO challenges introduced from Day 22. In the Morris water maze, the AR mixture reduced escape latency during the 3-day spatial training period and increased target quadrant exploration during the probe trial. In the passive avoidance test, it significantly prolonged step-through latency, confirming enhanced memory retention. Hippocampal biochemical assessments revealed that the AR mixture attenuated acetylcholinesterase activity, decreased malondialdehyde accumulation, and replenished acetylcholine levels. Furthermore, the formulation suppressed the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. AR mixture treatment attenuated the SCO-associated reductions in BDNF, p-TrkB, p-CREB, and PSD-95 expression and in ERK1/2 and Akt phosphorylation in the hippocampus. These findings suggest that the AR mixture improves cognitive and biochemical outcomes in SCO-treated rats, accompanied by changes in cholinergic function, lipid peroxidation, inflammation, and BDNF/TrkB-related signaling.