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.

Introduction: The ability of salt-processed Alismatis Rhizoma (SAR) (Alisma plantago-aquqtica L.) to nourish Yin and promote urination is stronger than that of Alismatis Rhizoma (AR). However, there are few studies focused on evaluating the quality of its medicinal materials. Objectives: This study aimed to identify potential quality markers (Q-markers) for SAR, thereby providing a more reliable basis for its quality control and clinical application. Methods: Q-markers were identified through fingerprinting and chemical pattern recognition analysis of 15 batches of SAR. The diuretic effects of these markers were then verified by network analysis and molecular docking. Results: HPLC fingerprints of 15 SAR batches were established, with similarity analysis showing values > 0.85 (0.852–0.990). Chemical pattern recognition identified six critical compounds contributing to SAR quality: alisol F, alisol C 23-acetate, alisol A, alisol A 24-acetate, alisol B 23-acetate, and an alisol O isomer (VIP > 1.0). Network analysis revealed 76 overlapping targets between these compounds and diuretic-related diseases, with core targets including non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), which were identified through protein–protein interaction (PPI) network analysis, with degrees of 27, 24, and 22, respectively. Key pathways involved were the EGFR tyrosine kinase inhibitor resistance pathway, calcium signaling pathway, tumor necrosis factor signaling pathway, etc. Molecular docking confirmed strong binding interactions between the Q-markers and the hub targets, particularly alisol B 23-acetate with MAPK1 (−60.10 kcal·mol⁻¹) and alisol A 24-acetate with EGFR (−46.14 kcal·mol⁻¹) and SRC (−48.86 kcal·mol⁻¹). The diuretic effects of SAR are likely mediated through anti-inflammatory actions and regulation of water–sodium balance via multi-target and multi-pathway mechanisms. Conclusion: This study provides a robust foundation for quality control and clinical application of SAR, though further in vivo validation is warranted.