Uncovering potential anti‐neuroinflammatory components of Modified Wuziyanzong Prescription through a target‐directed molecular docking fingerprint strategy

Graphical abstract Figure. No caption available. HighlightsA TMDF strategy was proposed to identify the potential anti‐neuroinflammatory components of MWP.120 possible structures were characterized by the SASC strategy.The prenylated flavonoids showed broad‐spectrum anti‐neuroinflammatory activities.IKK&bgr; and p38‐&agr; were the major anti‐neuroinflammatory targets.The Western blotting assay reinforced the reliability of the proposed TMDF strategy. ABSTRACT Neuroinflammation is a main factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer disease. Our previous studies indicated that the modified Wuziyanzong Prescription (MWP) can suppress neuroinflammatory responses via nuclear factor‐kappa B (NF‐&kgr;B) and mitogen‐activated protein kinases (MAPKs) signaling pathways. However, the anti‐neuroinflammatory components of MWP remain unclear. Herein, a target‐directed molecular docking fingerprint (TMDF) strategy, via integrating the chemical profiling and molecular docking approaches, was developed to identify the potential anti‐neuroinflammatory components of MWP. First, as many as 120 possible structures, including 49 flavonoids, 28 phenylpropionic acids, 18 amides, 10 carotenoids, eight phenylethanoid glycosides, four lignans, two iridoids, and one triterpenoid were deduced by the source attribution and structural classification‐assisted strategy. Then, their geometries were docked against five major targets of the NF‐&kgr;B and MAPKs signaling cascades, including p38‐&agr;, IKK&bgr;, ERK1, ERK2, and TRAF6. The docking results revealed diverse contributions of different components towards the protein targets. Collectively, prenylated flavonoids showed intensive or moderate anti‐neuroinflammatory activities, while phenylpropanoids, amides, phenylethanoid glycosides, lignans, and triterpenoids exhibited moderate or weak anti‐neuroinflammatory effects. The anti‐neuroinflammatory activities of four retrieved prenylated flavonoids were tested by Western blotting assay, and the results mostly agreed with those predicted by the docking method. These gained information demonstrates that the established TMDF strategy could be a rapid and feasible methodology to investigate the potential active components in herbal compound prescriptions.