Salicin ameliorates Alzheimer's-like pathology by modulation of NTSP/CSP/GLM pathways: An integrated in silico and in vivo approach.

Abstract

Alzheimer's disease (AD) is marked by modifiable and non-modifiable risk factors. Despite existing treatments, effective therapies to halt or reverse AD progression remain limited, highlighting the urgent need for new multitarget strategies. Phytotherapy as an anti-AD approach has emerged as an increasingly promising strategy in combating neurodegeneration, triggered by suppression of neuronal oxidation and inflammation. Salicin is a natural substance found in willow bark with anti-inflammatory and antioxidant effects. The present study investigates the protective effects of Salicin on neurodegeneration triggered by Scopolamine (Scop). Network pharmacology identified target pathways and genes involved in AD pathogenesis and suggested Salicin as a potential therapeutic agent. Molecular docking elucidated interactions within these target pathways. Scop (1 mg/kg, i.p.) induced memory dysfunction, and Salicin was administered at 12.5, 25, and 50 mg/kg (i.p.). Behavioral parameters were assessed for recognition and spatial memory using Novel Object Recognition (NOR) and Radial Arm Maze (RAM), respectively. AChE, BDNF, and PSEN-1 levels were studied as per in silico predictions, and microscopic changes in hippocampus and cortex were observed via histopathology. Top three pathways of Salicin were identified. The results of in silico and in vivo analyses demonstrate that the protective effects of Salicin are mediated through the Neurotrophin Signaling Pathway (NTSP), Cholinergic Synapse Pathway (CSP), and Glycerolipid Metabolism Pathway (GLM), which are critically implicated in AD progression. Relevant behavioral and histopathological improvements were observed. This study provides preliminary evidence supporting the potential of Salicin as a therapeutic candidate for AD, offering valuable direction for future research.