Cognitive impairment and decline in old age are primarily driven by the accumulation of age-related neuropathologies, and old age is thus the primary risk factor for
neurodegenerative diseases such as AD. Here, we investigated the effects of
Yizhi Qingxin formula (YQF) extract on
cognitive impairment in aged rats and determine the role of the
brain-derived neurotrophic factor (
BDNF)/
tropomyosin receptor
kinase B (TrkB) pathway underlying the
neuroprotective effects of the YQF extract. Fifty male Wistar rats were randomly divided into five groups: Control group, Model group,
Donepezil group, and YQF extract groups (treatment with YQF extract at two different doses).
After treatment with YQF extract for 8 weeks, learning and cognitive abilities were assessed using the Morris water maze. Morphological changes in the hippocampus were observed using
hematoxylin-
eosin. Activated microglia and astrocytes were assessed using immunohistochemistry. Expressions of
proteins and genes were examined using western blotting and real-time PCR. The results revealed that oral treatment with YQF extract dramatically improved spatial learning and memory ability and ameliorated histopathological and morphological characteristics in aged rats. YQF extract significantly increased
acetylcholine and
interleukin (IL)-10 levels but markedly decreased
amyloid-β
peptide,
tumor necrosis factor alpha (TNFα),
IL-2, and
IL-6 levels. In addition, it inhibited the excessive activation of microglia and astrocytes, downregulated the expressions of TNFα and
IL-2, and upregulated
nerve growth factor,
BDNF, and TrkB expressions. Furthermore, hippocampal extracellular signal-related
kinase (Erk) and
protein kinase B (Akt), the upstream signaling of
BDNF/TrkB, were also activated by treatment with YQF extract. Our findings indicate that YQF extract activates the
BDNF/TrkB pathway through the upregulation of Erk and Akt signaling, and the activated signaling pathway might contribute to the protective effects of YQF extract on
cognitive impairment in aged rats.