Bioactive compounds for neuroinflammation and neuropathic pain management: molecular and cellular mechanisms

Bioactive compounds are a promising multi-target strategy for managing neuroinflammation and chronic pain. Bioactive compounds such as Paeonol, Kaempferol, and Acteoside demonstrate significant analgesic and anti-inflammatory effects by inhibiting pro-inflammatory mediators (TNF-α, IL-1β, IL-6) and facilitating a phenotypic switch from pro-inflammatory M1-like to neuroprotective M2-like microglia. The aim of this review was to synthesize evidence on the molecular and cellular mechanisms by which bioactive compounds modulate neuroinflammation and neuropathic pain, and to evaluate the role of emerging systems biology tools in bridging the translational gap. Comprehensive body of literature on bioactive compounds derived from plant, marine, and traditional medicinal sources focuses on intracellular signaling pathways, including NF-κB, MAPK, and JAK2/STAT3, and their roles in microglial activation and cytokine production. Multi-omics analyses revealed that these compounds function as multi-target regulators rather than single-target agents, simultaneously addressing neuroinflammation, mitochondrial dysfunction, and oxidative stress. However, despite robust preclinical results, clinical translation is currently limited by poor bioavailability and blood-brain barrier permeability. This review further examined the integration of multi-omics technologies (transcriptomics, proteomics, and metabolomics), network pharmacology, and Artificial Intelligence (AI) in identifying compound-protein interactions. The transition from traditional medicine next-generation therapies requires a systems biology approach that combines nanotechnology-driven delivery systems with AI-guided personalized nutrition.