Integrating network pharmacology and an experimental validation strategy elucidates the protective effect and mechanism of callicarpa nudiflora against neuroinflammation

Abnormal activation of microglia promotes neuroinflammation (NI) in Alzheimer's disease (AD). Callicarpa nudiflora Hook et Arn. (CN) is a traditional Chinese herb with a wide range of clinical applications and definite anti-inflammatory effects. However, the anti-inflammatory action and mechanism of NI are not known. The purpose of this research was to survey whether CN could inhibit lipopolysaccharide (LPS)-induced inflammatory activation in BV-2 microglia. This study used a network pharmacology and pharmacophore model-based approach to explore the molecular mechanism of CN anti-NI by combining molecular docking and experimental validation. First, we screened the key active components and targets of CN anti-NI by network pharmacology. Then, the common structural features of these functional molecules in the treatment of neuroinflammation were predicted by 3D-QSAR pharmacodynamic modeling. Finally, the molecular mechanism of the active ingredient 5-hydroxy-3,7,4′-trimethoxyflavone (THF) against neuroinflammation was validated by molecular docking and in vitro experiments. In conclusion, this study established the structure–activity relationships of the active components of CN anti-NI and provided new insights into the pharmacological mechanisms of CN anti-NI at an integrative level.