Exploring the Multi-Target Effects of Valeriana officinalis in Alzheimer's Disease: a Network Pharmacology Approach

Alzheimer's disease (AD) is characterized by tau protein and amyloid-β buildup, which are linked to the molecular mechanisms underlying AD. Valeriana officinalis (VO) is a perennial herb that belongs to Caprifoliaceae family. The roots and rhizomes of this plant contain alkaloids, flavonoids, and glycosides, which are known for their neuroprotective effects in AD. To identify the molecular targets and anti-Alzheimer's properties of these phytoconstituents, a network pharmacology and in silico approach was employed. This method utilized pharmacokinetic and pharmacological data to analyze and elucidate anti-Alzheimer's mechanisms of VO. This research article identified 91 phytoconstituents and found 231 common targets between AD and VO. We selected the top 5 targets AKT1, Bcl2, IL-1B, IL6, and STAT3 based on degree, closeness, and betweenness centrality measures. We further conducted high-throughput virtual screening (HTVS), standard precision (SP) docking, extra precision (XP) docking, MMGBSA calculations, and ADMET analysis to identify potent phytoconstituents. Two compounds, CID10930 and CID442550, emerged as promising candidates for molecular dynamics simulations. These compounds were found to inhibit AKT1 by forming hydrogen bonds with vital amino acids Glu228, Ala230, Glu234, and Glu278. Specifically, the carbonyl and hydroxyl moieties of the phenyl ring and actinidine ring of the phytoconstituents played crucial roles in these interactions.