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, LIG_91 showed the top predicted AChE binding affinity (-8.5 kcal·mol⁻¹) and LIG_212 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&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.