[Ginsenoside Rg1 modulates BV2 microglial activation and neuroinflammation via the JAK2/STAT3 pathway]

Objective To investigate how ginsenoside Rg1 regulates microglia-mediated neuroinflammation through the JAK2/STAT3 pathway following ischemic stroke. Methods Potential Rg1 targets were identified by network pharmacology, and molecular docking was used to evaluate ligand-target interactions. BV2 microglia were cultured and divided into four groups: Control, OGD, OGD+Rg1, and OGD+Rg1+AG490 (co-treatment with the JAK2 inhibitor AG490). Western blot and dual immunofluorescence staining were used to assess the expression of phosphorylated JAK2 (p-JAK2), phosphorylated STAT3 (p-STAT3), and downstream inflammatory mediators inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α). Results Network pharmacology revealed 16 overlapping targets between Rg1 and ischemic stroke, with STAT3 identified as a key node in the JAK2/STAT3 pathway. Molecular docking showed strong binding affinity between Rg1 and core targets. Rg1 treatment significantly reduced the expression of p-JAK2, p-STAT3, iNOS, and TNF-α compared with the OGD group. The AG490 co-treatment group exhibited similar inhibitory effects, with no significant difference from Rg1 alone. Conclusion Ginsenoside Rg1 suppresses the expression of iNOS and TNF-α in activated BV2 microglia, likely by inhibiting phosphorylation of the JAK2/STAT3 pathway.