Saraswata Ghrita mitigates AlCl₃- and D-galactose–induced cognitive deficits in a murine Alzheimer’s-like model: In silico and in vivo insights

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive decline linked to cholinergic dysfunction, oxidative stress, and neuroinflammation. Saraswata Ghrita (SG), a classical Ayurvedic formulation, was evaluated using an integrated in silico-in vivo workflow focusing on acetylcholinesterase (AChE) and related pathways. METHODS: SG constituents were profiled by GC-MS/MS and HR-LCMS/MS-QTOF. BBB-permeable, drug-like candidates were prioritized (SwissADME/BOILED-Egg) and evaluated by docking and molecular dynamics. In vivo, mice received AlCl₃ (4 mg/kg, i. p. ) + D-galactose (50 mg/kg, i. p. ) for 60 days; SG (3, 6, 12 mL/kg, p. o. ) or donepezil (0. 5 mg/kg, i. p. ) was administered on days 31-60. Behavioral, biochemical, and histological endpoints were assessed (n = 6/group). RESULTS: In silico, LIG₉1 showed the top predicted AChE binding affinity (-8. 5 kcal·mol⁻¹) and LIG₂12 scored -7. 8 kcal·mol⁻¹ (supportive evidence). AlCl₃+D-galactose impaired cognition (MWM day-4 ELT 85. 8 ± 5. 3 s; TSTQ 34. 6 ± 2. 2 s). SG 12 mL/kg improved MWM performance (ELT 44. 1 ± 3. 2 s, ∼49 % lower vs model; TSTQ 50. 1 ± 2. 8 s, ∼45 %higher), while donepezil produced greater improvement (ELT 26. 7 ± 2. 4 s, ∼69 % lower; TSTQ 58. 1 ± 5. 4 s, ∼68 %higher). SG 12 mL/kg reduced oxidative stress (TBARS 12. 93 ± 1. 58 → 8. 84 ± 0. 52 nM/mg, ∼32 % decrease) and improved antioxidant status (GSH 7. 52 ± 0. 48 → 11. 10 ± 0. 48 µM/mg, ∼48 % increase). SG also attenuated neuroinflammation (IL-6 211. 1 ± 10. 6 → 165. 0 ± 23. 6 pg/mL, ∼22 % decrease; TNF-α 179. 3 ± 8. 7 → 133. 7 ± 7. 8 pg/mL, ∼25 % decrease; IL-10 12. 3 ± 1. 0 → 30. 2 ± 5. 2 pg/mL, ∼146 % increase) and lowered AChE activity (10. 61 ± 0. 61 → 8. 49 ± 0. 49 µM/min/mg, ∼20 % decrease). H further quantitative histology and standardized-formulation studies are warranted.