Achyranthes japonica Nakai (USL) is a traditional medicinal plant with known antioxidant and anti-inflammatory properties; however, its efficacy against dry eye disease (DED) remains unclear. This study investigated the protective effects of USL against DED using an integrated network pharmacology and experimental approach. Chemical constituents of USL were identified by HPLC–MS, and network pharmacology analysis revealed 96 common targets shared between USL and DED, including 30 hub targets primarily associated with inflammasome activation and apoptosis-related pathways. Molecular docking analysis demonstrated favorable binding affinities between major USL constituents and key inflammatory proteins, including NLRP3 and caspase-3.
In vitro, USL significantly suppressed hyperosmolar stress–induced NF-κB activation and reduced the expression of pro-inflammatory cytokines, including IL-1β, TNF-α, MMP9, IL-33, and IL-13, in human conjunctival cells (n = 3). In vivo, oral administration of USL (100 and 250 mg/kg) significantly improved ocular surface parameters in a rat model of DED (n = 7 per group), increasing tear volume from 2.75 ± 1.25 to 5.60 ± 1.36 mm (p < 0.05), restoring conjunctival goblet cell density from 201.7 ± 46.9 to 267.1 ± 46.3 cells/100 μm (p < 0.05), and alleviating corneal surface irregularities. In addition, USL markedly reduced inflammatory markers, including MPO, CXCR1, NLRP3, and IL-17, in conjunctival tissues.
Taken together, these findings demonstrate that USL exerts protective effects against DED by modulating inflammatory and apoptotic pathways, particularly through regulation of inflammasome-associated signaling, and may serve as a promising plant-derived functional ingredient for improving ocular surface health.
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