Protective effects and mechanisms of Panax notoginseng saponins against gp120-induced cognitive impairment: a network pharmacology and metabolomics study.

OBJECTIVE

This study investigates Panax notoginseng saponins (PNS) as a potential treatment for gp120-induced HIV-associated neurocognitive disorder (HAND), in light of the limited efficacy of current therapies.

METHODS

A rat model of gp120-induced HAND was established. Cognitive function was evaluated using the Morris water maze and novel object recognition tests. Hippocampal metabolomics and network pharmacology were integrated to identify critical pathways and targets. The expression of core targets was validated by enzyme-linked immunosorbent assay (ELISA).

KEY FINDINGS: PNS administration significantly mitigated gp120-induced cognitive deficits, demonstrated by shortened escape latency and an increased number of platform crossings in the Morris water maze. Network pharmacology analysis pinpointed the NOD-like receptor signaling pathway as the principal target, a finding corroborated by metabolomics data. ELISA confirmed that PNS decreased hippocampal levels of the pro-inflammatory cytokines IL-1β, IL-6, and CCL2 while upregulating the anti-apoptotic protein Bcl2.

CONCLUSION

PNS confers neuroprotection against gp120-induced cognitive impairment by modulating the NOD-like receptor signaling pathway, which suppresses neuroinflammation and inhibits apoptosis.