Anti-Alzheimer’s Studies on β-Sitosterol Isolated from Polygonum hydropiper L.

Abstract

The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer's disease (AD). In search of new anti-AD drugs, β-sitosterol isolated from <i>Polygonum hydropiper</i> was subjected to <i>in vitro, in vivo</i>, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer's agent. The <i>in vitro</i> AChE, BChE inhibitory potentials of β-sitosterol were investigated following Ellman's assay. The antioxidant activity was tested using DPPH, ABTS and H₂O₂ assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. β-sitosterol was tested for <i>in vivo</i> inhibitory potentials against cholinesterase's and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of β-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable <i>in vitro</i> and <i>in vivo</i> cholinesterase inhibitory effects were observed in the β-sitosterol treated groups. β-sitosterol exhibited an IC₅₀ value of 55 and 50 μg/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of β-sitosterol with the target enzyme and further support the <i>in vitro</i> and <i>in vivo</i> results. In the antioxidant assays, the IC₅₀ values were observed as 140, 120, and 280 μg/ml in the DPPH, ABTS and H₂O₂ assays respectively. The free radicals load in the brain tissues was significantly declined in the β-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, β-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that β-sitosterol is a potential compound for the management of memory deficit disorders like AD.