AnMei decoction ameliorates cognitive impairment in rats with chronic sleep deprivation by mitigating hippocampal neuroinflammation and restoring synaptic architecture.

SIGNIFICANCE OF ETHNOPHARMACOLOGY: AnMei Decoction (AMD) is a renowned herbal prescription that has been widely demonstrated to have positive therapeutic effects on sleep disorders, depression, and cognitive impairments. However, the molecular mechanisms underlying AMD's resistance to sleep deprivation-induced cognitive impairment remain to be further investigated.

RESEARCH

OBJECTIVE

To clarify whether AMD may alleviate neuroinflammation by inhibiting NLRP3/Caspase1 signaling pathway and repair neuronal damage by regulating BDNF/TrkB pathway, thereby improving cognitive dysfunction in rats with chronic sleep deprivation.

MATERIALS AND

METHODS

LC-MS/MS was used to detect the active components in AMD. After behavioral tests, HE staining, Nissl staining, immunofluorescence, immunohistochemistry, transmission electron microscopy, and Golgi staining were performed to assess the effects of AMD on chronic sleep deprivation. Western blot was used to detect the expression of hippocampal proteins NLRP3, Caspase-1, BDNF, p-TrkB, TrkB, Bax, Bcl-2, GAP43, PSD95, SNAP25, SYN, STX1A, and VAMP2. Hippocampal transcriptome sequencing was employed to observe differentially expressed genes after AMD intervention.

RESULTS

A total of 15 active components were identified from the AMD extract. AMD effectively improved the exploration and learning and memory abilities of sleep-deprived rats. AMD reduced neuroinflammation by inhibiting the NLRP3/Caspase-1 pathway and repaired neuronal damage by regulating the BDNF/TrkB pathway. Simultaneously, AMD upregulated the expression of BDNF, p-TrkB, Bcl-2, GAP43, PSD95, SNAP25, SYN, STX1A, and VAMP2 proteins and inhibited the expression of NLRP3, Caspase-1, and Bax proteins. Analysis of GO and KEGG pathway enrichment for the differentially expressed inflammation-related pathways may be involved in the therapeutic mechanism of AMD on sleep deprivation.

CONCLUSION

AMD can effectively inhibit the NLRP3/Caspase1 signaling pathway to alleviate neuroinflammation, regulate the BDNF/TrkB pathway to maintain hippocampal neuronal viability, repair synaptic structural damage, and improve cognitive impairment in the sleep deprivation model.