Therapeutic Potential of a Tectorigenin Derivative (TED) in Herpetic Stromal Keratitis: Antiviral and lmmunomodulatory Mechanisms

Objectives: In this study, the anti-HSV-1 effects of TED were investigated in vitro and in vivo, its therapeutic efficacy against herpetic stromal keratitis (HSK) was evaluated, and its mechanism of action was examined. Methods: We assessed the cytotoxicity and anti-HSV-1 activity of TED in Vero cells using CCK-8 and plaque assays. The HSK model mice received TED (2.5, 5, or 15 mg/kg), and symptom progression was monitored. The therapeutic effects were evaluated through HE staining, corneal immunofluorescence, and HSV-1 gB quantification. Mechanistic studies were performed to examine the expression of TLR pathway genes, CD4+/CD8+ T-cell infiltration in the cornea and draining lymph nodes, and dendritic cell activation. Results: TED showed potent anti-HSV-1 activity in vitro and ameliorated HSK in mice, improving body weight and reducing corneal pathology and the incidence of encephalitis. It decreased HSV-1 loads in the cornea, trigeminal ganglion, and brain while modulating cytokines (downregulating IFN-α/γ, TNF-α, and IL-1β and upregulating IL-10). TED suppressed the TLR pathway (TLR2/3/9, TRAF6, IRF3, and NF-κB) in the corneal epithelium and reduced CD4+/CD8+ T-cell and dendritic cell infiltration while increasing the number of CD4+ T cells in the lymph nodes. Conclusions: TED has significant anti-HSV-1 activity and effectively treats HSK by reducing viral loads, improving symptoms, and modulating immune responses through TLR pathway inhibition and immune cell regulation, suggesting its potential as an HSK therapeutic.