Introduction: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment. Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH. Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.

Salt-processed Alismatis Rhizoma (SAR) is extensively used in clinical practice and exhibits a more robust urination-promoting effect than Alismatis Rhizoma (AR). This study employed ultra-performance liquid chromatography–quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and pattern analysis to compare the terpenoids between AR and SAR. Additionally, this study compared the effects of AR and SAR on the gene expression in the kidneys of the rat model of edema (syndrome of kidney Yin deficiency) by transcriptomics to decipher the mechanism of salt processing. Materials and methods: AR and SAR were extracted by ultrasonication, and data were collected by UPLC-Q-TOF-MS in the positive ion mode. Transcriptome sequencing was employed to determine the gene expression levels of the rat model treated with AR and SAR, and the differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was performed for the DEGs. The protein-protein interaction (PPI) network was built, on the basis of which the core targets were screened out. Finally, real-time quantitative polymerase chain reaction (RT-PCR) was conducted to verify the core targets. Results: A total of 63 terpenoids were detected in AR and SAR, and salt processing had a significant effect on the content of terpenoids. AR and SAR mainly participated in the regulation of inflammation and immune responses, and SAR regulated more DEGs than AR. Additionally, SAR exerted more extensive regulatory effects on the targets than AR. Conclusion: Salt processing mainly changes the content of chemical compounds in AR, which may indirectly optimize the proportion of the main compounds to enhance the therapeutic effect while reducing the toxicity. AR and SAR mainly ameliorate the edema due to kidney Yin deficiency by reducing inflammation and improving immunity. Finally, SAR regulates more genes and signaling pathways and exerts more extensive regulatory effects than AR.