Neuroprotective effects of aqueous extract of Pterocarpus mildbraedii Harms. on some biochemical markers in Alzheimer's disease using an AlCl3-induced rat model: Integrated ADMET, network pharmacology, molecular docking, and in vivo experimental validation.

ETHNOPHARMACOLOGY RELEVANCE: Neurodegenerative diseases such as Alzheimer's often lack effective conventional treatments. Phytotherapy is emerging as a promising approach to managing these conditions. Pterocarpus mildbraedii Harms. (P. mildbraedii), a plant from the Fabaceae family, which is traditionally used to treat convulsions, headaches, and fever. This study is designed to evaluate the neuroprotective effects of the aqueous extract of Pterocarpus mildbraedii Harms. on biochemical markers of Alzheimer's disease in an AlCl3-induced rat model using integrated ADMET, network pharmacology, molecular docking, and in vivo validation.

METHODS: We employed network pharmacology and in silico molecular docking to identify bioactive compounds and assess their binding affinities to key proteins: VCP, MAPK1, MMP9, PTGS1, IL6, and AR. The in vivo experiment lasted 56 days, with 30 animals divided into 5 groups (n = 6 per group). They received daily oral doses of distilled water (10 mL/kg), AlCl3 (75 mg/kg), Donepezil (5 mg/kg) after AlCl3, or P. mildbraedii bark water extract at 150 mg/kg (PM 150) and 300 mg/kg (PM 300) following AlCl3. On Days 23 and 51, all animals underwent open-field and Morris water maze tests. On Day 57, animals were sacrificed, and calcium levels, oxidative markers, and neurotransmitter levels were measured in homogenates from the amygdala, hippocampus, and prefrontal cortex. Histopathological analysis of the hippocampus and amygdala was also conducted.

RESULTS: In silico studies showed that the plant compounds pterocarpan and liquiritigenin bound strongly to VCP, MAPK1, and MMP9, with binding energies lower than those of reference inhibitors, indicating greater stability. In vivo, AlCl3 caused anxiety, locomotor issues (p < 0. 001), memory impairment (p < 0. 001), and disrupted GABA, ACh metabolism, and AChE activity. It also reduced antioxidant levels (p < 0.001), increased pro-oxidants (p < 0.001), and elevated calcium and Tau protein levels compared to the normal control. Treatment with Pterocarpus mildbraedii extract mitigated these effects, reducing anxiety and enhancing memory, locomotion, ACh, and GABA levels, as well as AChE activity. The extract notably decreased Tau protein and MDA concentrations by 80. 57% in the amygdala, 63. 80.57% in the prefrontal cortex, and 63.73. 50% in the hippocampus, and nitrites. It also significantly increased protein levels, GSH (by 6.95-fold in the amygdala, 80.48% in the prefrontal cortex, and 85.75% in the hippocampus), SOD, and catalase activities across brain regions compared with the AlCl3-treated group.

CONCLUSION: These findings suggest that Pterocarpus mildbraedii extract, with its antioxidant, anti-amnesic, and anxiolytic properties, offers neuroprotection and may have neuroprotective effects in Alzheimer 's-like neurotoxicity.