Anti-neuroinflammatory and neuroprotective effects of sweroside and swertiamarin from Swertia bimaculata in an in vitro microglial activation model.

Neuroinflammation, driven by microglial overactivation and subsequent pro-inflammatory cascades, is a hallmark of neurodegenerative pathologies. This study presents a phytochemical investigation of Swertia bimaculata (Siebold & Zucc.) Hook. f. & Thomson ex C. B. Clarke (S. bimaculata), resulting in the isolation of 11 monomeric compounds, including secoiridoid glycosides, xanthones, and flavonoids. An integrated pipeline of network pharmacology and molecular docking identified Sweroside (SS) and Swertiamarin (ST) as key bioactive constituents targeting core inflammatory proteins like NLRP3, Caspase-1, and IL-1β. Experimental validation in LPS/ATP-activated BV2 cells demonstrated that SBE, SS, and ST significantly suppressed mRNA expression of iNOS and the NLRP3 inflammasome while reducing reactive oxygen species (ROS) and intracellular Ca2+ accumulation. Mechanistically, these effects were mediated by the activation of the Nrf2/HO-1 signaling pathway. Furthermore, in an HT-22 neuron co-culture system, these components exhibited neuroprotective effects in this in vitro co-culture system by normalizing serotonin (5-HT) levels and modulating 5-HT-2A expression. Further in vivo animal studies are required to determine whether the cellular effects observed in this study translate to therapeutic benefits against neurodegenerative and mood disorders in vivo.