BACKGROUND:Vascular dementia (VD) is a major cause of cognitive decline associated with cerebrovascular dysfunction, and effective therapeutic strategies remain limited. Ligusticum wallichii is a traditional medicinal herb with neuroprotective activity. METHODS:This study investigated the protective effects of L. wallichii against VD by combining network pharmacology with experimental validation. Active constituents and putative targets of L. wallichii were identified using the TCMSP database and SwissTargetPrediction platform, whereas VD-related genes were collected from GeneCards, DisGeNET and OMIM. Protein-protein interaction analysis, Gene Ontology annotation, KEGG pathway enrichment and molecular docking were used to prioritize targets and pathways. The extract used for animal studies was profiled by HPLC. A rat model of VD induced by permanent bilateral common carotid artery occlusion was used for in vivo validation. RESULTS:Seven database-derived compounds and 450 putative targets were identified, of which 177 overlapped with VD-related genes. Network analysis highlighted AKT1, TNF, EGFR, BCL2 and CASP3 as hub targets associated with oxidative stress- and apoptosis-related signalling. HPLC detected ferulic acid, senkyunolide H, senkyunolide I, senkyunolide A and Z-ligustilide in the extract. In vivo, L. wallichii reduced neurological deficit scores, improved spatial learning and memory, alleviated hippocampal neuronal injury, restored cholinergic balance and increased antioxidant indices. Western blotting showed restoration of AKT phosphorylation, increased Bcl-2 expression, reduced Bax and Caspase-3 expression, and recovery of the Bcl-2/Bax ratio after treatment. CONCLUSIONS:These findings associate the neuroprotective effects of L. wallichii in VD with AKT activation, attenuation of oxidative stress and inhibition of Bcl-2/Bax/Caspase-3-related apoptosis.
BACKGROUND:Systemic lipopolysaccharide (LPS)-induced inflammation can disrupt cerebral redox homeostasis and nicotinamide adenine dinucleotide (NAD)-related metabolism, but the extent to which a multimodal nutritional intervention can attenuate these changes remains unclear. OBJECTIVE:This study compared the effects of phycocyanin-derived oligopeptides (PC-O), zinc (Zn), selenium (Se), and their combined administration on whole-brain NAD-related metabolites, oxidative status, antioxidant enzyme activities, selected mRNA markers, and the protein abundance of representative neurotrophic, synaptic, astroglial, and inflammatory markers after low-dose LPS exposure. METHODS:Forty-two male BALB/c mice were allocated to six groups (n = 7/group). PC-O, Zn, Se, or PC-O + Zn + Se was administered orally for 14 days before intraperitoneal LPS challenge (0.04 mg/kg). RESULTS:LPS was associated with lower concentrations of the four NAD-related analytes and lower antioxidant enzyme activities, higher MDA, reduced BDNF, NGF, Synapsin-1, PGC-1α, and TFAM transcripts, and increased GFAP, IL-1β, and IL-6 transcripts (p < 0.05). Western blot analysis further showed lower BDNF and Synapsin I protein abundance and higher GFAP, IL-1β, and IL-6 protein abundance following LPS exposure (p < 0.05). The single-supplements produced endpoint-dependent changes, whereas the PC-O + Zn + Se group showed the most consistent attenuation across the biochemical, transcript, and selected protein outcomes. CONCLUSION:Low-dose LPS was associated with coordinated disturbances in brain NAD-related metabolism, redox balance, and inflammatory signaling. The combined intervention produced a broader biochemical and molecular response than the single interventions; however, mechanistic, histological, behavioral, and translational studies are required before clinical relevance can be inferred.
