This study aimed to investigate the mechanisms by which Acanthopanax senticosus extract (ASH) exerts effects onα-synuclein (α-syn) overexpressing transgenic mouse model of Parkinson's disease (PD), with a focus on its regulation of brain lipid metabolism. Twenty PD model mice were randomly assigned to a model group or an ASH treatment group (45.5 mg·kg-1 by gavage for 4 weeks), and 10 C57BL/6 mice served as a normal control group. Behavioral assessments revealed that, compared with controls, PD model mice showed prolonged pole test time, reduced spontaneous locomotor activity, shorter latency to fall in the rotarod test, and decreased total distance traveled in the open field test. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), caspase-9 were significantly elevated, B-cell lymphoma-2 (Bcl-2), and proliferating cell nuclear antigen (PCNA) expression was reduced, and marked neuronal damage was observed in brain tissue. ASH intervention significantly improved these behavioral and biochemical parameters and attenuated neuronal injury. Untargeted lipidomics analysis revealed significant alterations in sphingomyelin (SM), ceramide (Cer), phosphatidylcholine (PC), and phosphatidylserine (PS) across multiple brain regions (cortex, substantia nigra, cerebellum, and striatum) in PD mice, which were notably restored by ASH treatment. Pathway analysis indicated that these metabolites were predominantly involved in sphingolipid metabolism. Western blot further demonstrated that ASH downregulated the expression of key sphingolipid metabolic enzymes serine palmitoyltransferase long-chain base subunits 1 and 2 (SPTLC1 and SPTLC2) and upregulated UDP-glucose ceramide glucosyltransferase (UGCG), β-galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2), thereby suppressing abnormal SM and Cer accumulation in the substantia nigra and elevating PS and PC levels in the striatum. Spearman's correlation analysis supported the modulatory effect of ASH on brain lipid metabolic profiles. In conclusion, ASH improves behavioral deficits, exerts anti-inflammatory effects, and regulates sphingolipid metabolism to correct disordered lipid profiles, thereby providing neuroprotective effects in PD mice.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |