Abstract Title:

Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver.

Abstract Source:

Proc Natl Acad Sci U S A. 2012 Jan 30. Epub 2012 Jan 30. PMID: 22308347

Abstract Author(s):

Neha Sehgal, Alok Gupta, Rupanagudi Khader Valli, Shanker Datt Joshi, Jessica T Mills, Edith Hamel, Pankaj Khanna, Subhash Chand Jain, Suman S Thakur, Vijayalakshmi Ravindranath

Article Affiliation:

Division of Molecular and Cellular Neuroscience, National Brain Research Centre, Nainwal Mode, Manesar, Haryana 122050, India.

Abstract:

A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation ofβ-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Aβ and a decrease in brain Aβ monomer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Aβ levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.

Study Type : Transgenic Animal Study

Print Options


Key Research Topics

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2024 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.