ETHNOPHARMACOLOGICAL RELEVANCE: Age-related cognitive impairment is a common neurodegenerative disease. Shenxian zhou (SXZ) is a Traditional Chinese Medicine formulation noted for its health-preserving properties, as documented in the Meditating-and-Breathing Methods, Dunhuang manuscript P.3810. Contemporary studies indicate that SXZ may possess anti-aging properties and enhance cognitive function. However, the specific effects and mechanisms of SXZ in addressing age-related cognitive impairment require further investigation.
AIM OF THE STUDY: This study utilized aged rats to explore the therapeutic effects of SXZ on cognitive impairment and to elucidate its potential mechanisms.
MATERIALS AND METHODS: This study investigated the main compounds of SXZ utilizing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS). Following the administration of SXZ to naturally aged rats, behavioral tests were conducted using maze tests, and histopathological changes in the hippocampus were observed using hematoxylin-eosin (H&E) staining and Nissl staining. Transcriptome sequencing technology was then employed to investigate the mechanism through which SXZ enhanced cognitive function in aged rats. Furthermore, immunofluorescence staining, Western blotting (WB), and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to confirm the findings of transcriptome sequencing.
RESULTS: Behavioral test showed that SXZ could improve the learning and memory ability of aging rats; Pathological findings showed that SXZ ameliorated structural impairment in the hippocampus of aged rats and enhanced the number of Nissl bodies; In the transcriptome studies, Gene Ontology (GO) enrichment analysis suggested that SXZ modulated key biological processes, including lysosomal localization, mitochondrial membrane function, and the regulation of autophagosomes and autophagy. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, mitophagy and necroptosis might be critical mechanisms by which SXZ improved cognitive impairment in aged rats. Transmission electron microscopy (TEM) showed that SXZ alleviated mitochondrial structural impairment and increased the number of autolysosomes. Furthermore, molecular biology results indicated that SXZ significantly enhanced mitochondrial function, regulated the expression of key molecules in the mitophagy and necroptosis pathways, and consequently inhibited the inflammatory response.
CONCLUSION: This study demonstrated that SXZ was effective in preventing and treating cognitive impairment in aged rats. Its specific mechanism was highly associate with the activation of mitophagy, alleviation of mitochondrial impairment-induced necroptosis, and the decrease of inflammatory damage in the hippocampus of aged rats.
