Panax quinquefolium saponins protects neuronal activity by promoting mitophagy in both in vitro and in vivo models of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE

In the realm of traditional Chinese medicine, Panax quinquefolius L. has garnered significant attention for its potential to treat various ailments associated with deficiencies, including qi, blood, and kidneys. As its primary bioactive constituent, Panax quinquefolius saponins (PQS) have the potential therapeutic role of Alzheimer's disease (AD) treatment, but with unclear mechanisms of action. Meanwhile, AD is considered as a common dementia disease with kidney insufficiency and deficiency by traditional medicine, and often accompanied by autophagy in modern medical research.

AIM OF THE STUDY

This study aimed to investigate the therapeutic effects of PQS on AD through the regulation of mitophagy.

MATERIALS AND METHODS

The chemical constituents of PQS were characterized using the UPLC-QTOF-MS technique. After that, the HT22 cell line was used to establish the D-galactose-induced cell model, and the SAMP8 mice model of AD was also employed. Cell viability was assessed using the CCK-8 assay, ROS detection, JC-1 staining, Mito-tracker Red and LC3 staining, and Mito-tracker Green and Lyso-tracker Red staining were used to assess levels of mitophagy. The Morris Water Maze (MWM) was used for the experimental evaluation of learning and memory abilities in mice. Subsequently, the mechanism was studied by pathological staining and western blotting.

RESULTS

Fifty-eight triterpenoid saponins were identified from PQS, and PQS alleviated D-galactose-induced HT22 cell death and increased intracellular levels of mitochondrial autophagy-related factors. In vivo, PQS significantly improved cognitive deficits and mitigated AD-like pathological features by activating the mitophagy mechanism. Furthermore, PQS may promote Pink1/Parkin-mediated mitophagy by activating the AMPK/mTOR/ULK1/DRP1 and SIRT1/PGC-1α pathways.

CONCLUSION

In conclusion, PQS have demonstrated the potential to mitigate mitochondrial dysfunction and enhance cognitive function in AD through the activation of mitophagy. This promising strategy holds great promise for the treatment of AD.