Pyranocoumarin-enriched residue extracts of Angelica gigas suppress NLRP3 inflammasome activation and neuroinflammation.

BACKGROUND

Angelica gigas Nakai is a medicinal plant rich in pyranocoumarins with well-documented anti-inflammatory and neuroprotective properties. However, the pharmacological potential of residues remaining after conventional aqueous extraction remains largely unexplored. This study investigated the phytochemical composition and anti-neuroinflammatory activity of residue-derived extracts of A. gigas, focusing on the regulation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome.

METHODS AND

RESULTS

A water extract (PO6W), an ethanol extract (PO6E), and a residue-derived ethanol extract (PO6RE) were chemically characterized and evaluated in lipopolysaccharide-stimulated BV2 microglial cells and an LPS-induced mouse model. Molecular docking, surface plasmon resonance, and MCC950 intervention were used to investigate the association between decursin and NLRP3 signaling. Despite prior aqueous extraction, the residual biomass retained substantial amounts of pyranocoumarins, and subsequent ethanol extraction yielded PO6RE with the highest levels of decursin and decursinol angelate. PO6RE significantly suppressed the expression levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, cleaved caspase-1, and interleukin-1β in BV2 cells and reduced microglial activation in vivo. Decursin showed measurable binding to NLRP3 and reduced NLRP3 expression and interleukin-1β production.

CONCLUSIONS

A. gigas biomass remaining after aqueous extraction retains bioactive pyranocoumarins that can be recovered by subsequent ethanol extraction. The resulting residue-derived extract exhibited anti-neuroinflammatory activity associated with NLRP3 inflammasome signaling, highlighting extraction residues as an underutilized and potentially sustainable source of bioactive phytochemicals.