A phenolic acid glyceride dimer isolated from Lilium brownii exerts neuroprotective effects in Parkinson's disease by modulating the p62-Keap1-Nrf2 signalling pathway.

UNLABELLED: Lilium brownii is a plant that can be used for medicinal and food purposes. 1-O-p-coumaroyl-3-O-feruloyl glycerol (CF) is a phenolic acid glycerol dimer isolated from Lilium brownii.

OBJECTIVE

This study aims to evaluate the neuroprotective effects of CF and elucidate the possible molecular mechanisms underlying its neuroprotective effects through in vivo and in vitro models of Parkinson's disease.

METHODS

1-methyl-4-phenylpyridinium ions (MPP+) was used to establish in vivo and in vitro models of Parkinson's disease (PD); flow cytometry was used to detect intracellular reactive apoptosis rates and cell cycle distribution. Western blot aalysis was used to assess the expression levels of relevant proteins. Molecular docking technology was used to evaluate the binding affinity of CF with Sequestosome 1 (P62), etc. Behavioral experiments assessed motor ability and cognitive function in PD mice, and tissue sections were examined to observe the number of neurons in the substantia nigra region of the mouse brain.

RESULTS

Following CF administration, the apoptosis rate and reactive oxygen species (ROS) levels in PC12 cells were significantly reduced. CF markedly upregulated the expression of proteins including dopamine, tyrosine hydroxylase, brain-derived neurotrophic factor (BDNF), while simultaneously downregulating the expression of proteins such as α-synuclein. Molecular docking results demonstrated favorable affinity between CF and proteins including p62. This compound not only ameliorated motor and cognitive impairments in Parkinson's disease mice but also markedly increased neuronal numbers within the substantia nigra region of these animals.

CONCLUSION

CF exerts a neuroprotective effect in Parkinson's disease by modulating the p62-Keap1-Nrf2 signalling pathway.