Badal_2026_Brain.Res.Bull_235_111742

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, LIG_91 showed the top predicted AChE binding affinity (-8.5 kcal.mol) and LIG_212 scored -7.8 kcal.mol (supportive evidence). AlCl+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 microM/mg, -48 % increase). SG also attenuated neuroinflammation (IL-6 211.1 +/- 10.6 165.0 +/- 23.6 pg/mL, -22 % decrease; TNF-alpha 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 microM/min/mg, -20 % decrease). H&E micrographs qualitatively suggested reduced cortical neuronal degeneration. CONCLUSIONS: SG administration was associated with improved cognition and partial normalization of cholinergic, oxidative, and inflammatory markers in this model. Computational findings support possible AChE engagement but are not definitive; further quantitative histology and standardized-formulation studies are warranted.