Investigation of the Efficacy of Qin Pi Extract in Alleviating Dry Eye Disease in Murine Models and Its Association with Suppression of Lymphangiogenesis

Qin Bing eye drops, a traditional Chinese medicine-based in-hospital preparation, were historically indicated for the treatment of conjunctivitis, keratitis, and photokeratitis. This study aimed to develop Qin Pi extract (QP-E) using a proprietary extraction method, and to evaluate the therapeutic efficacy of QP-E alone, QP-E combined with Bing Pian (BP), and an ophthalmic formulation (QP-D) comprising both constituents in a preclinical model of dry eye disease (DED). DED was induced in mice via subcutaneous scopolamine administration alone, whereas a more robust dry eye phenotype was established in rats through combined treatment with scopolamine and environmental stressors. Ocular surface evaluation included measurement of tear secretion volume and corneal fluorescein staining scores. The results demonstrated that both QP-E monotherapy and the QP-E–BP combination significantly ameliorated key pathological features of DED, including tear film instability and corneal epithelial damage. QP-D—formulated with rationally optimized concentrations of QP-E and BP—significantly enhanced basal tear secretion and attenuated corneal epithelial injury in both murine and rat dry eye models. Mechanistic investigations revealed that QP-E treatment markedly inhibited VEGF-C secretion from classically activated (M1) macrophages, suppressed phosphorylation-dependent activation of the VEGF-C/VEGFR-3 signaling axis, and consequently impaired lymphatic endothelial cell migration and in vitro tube formation. These correlative findings indicate that QP-E may partially alleviate DED by suppressing lymphangiogenesis; however, direct causal evidence—such as genetic ablation of VEGF-C or pharmacological inhibition of VEGFR-3—was not established in the present study. Collectively, our data yield a testable mechanistic hypothesis and propose a novel therapeutic strategy targeting lymphatic remodeling for DED intervention.