Integrative Evaluation Of Jue-Ming Granules For Dry Eye Disease: Evidence-Based Preclinical Insights Into Multi-Target Mechanisms

Dry eye disease (DED) is a prevalent ocular surface disorder characterized by chronic inflammation and limited long-term therapeutic options. Jue-Ming Granules (JMGs), a modified herbal formulation composed of drug–food homologous and health-grade ingredients, represent a promising integrative intervention with multi-target anti-inflammatory potential. This study aimed to systematically investigate the pharmacological mechanisms and therapeutic efficacy of JMGs in DED treatment using a multilevel preclinical approach.

Preclinical experimental study

Active compounds and therapeutic targets of JMGs were identified via network pharmacology platforms (TCMSP, HERB, GeneCards, OMIM). GO, KEGG enrichment, and protein–protein interaction (PPI) analyses were conducted to identify key pathways. Molecular docking (AutoDock Vina, PyMOL) evaluated compound–target interactions. In vitro experiments were conducted using benzalkonium chloride–injured human corneal epithelial (HCE) cells, while in vivo efficacy was evaluated in a scopolamine hydrochloride- and desiccation-induced DED mouse model. Western blot analysis was performed in both HCE cells and corneal tissues to assess pathway-related protein expression, and pathway involvement was further examined using a PI3K-specific inhibitor.

Quercetin, caffeine, and luteolin were identified as major active compounds targeting key inflammation-related proteins (AKT1, TNF, IL-6). JMGs significantly enhanced HCE cell viability and downregulated proinflammatory cytokine expression. In vivo, JMGs promoted tear secretion, reduced corneal damage, preserved goblet cell density, and suppressed inflammatory markers (TNF-α, IL-6, IFN-γ). Western blot analysis demonstrated that JMGs markedly inhibited the phosphorylation of PI3K, AKT, and NF-κB p65 in both HCE cells and corneal tissues. Pharmacological inhibition of PI3K partially attenuated the protective effects of JMGs, supporting the functional involvement of the PI3K/AKT/NF-κB signaling axis.

JMGs provide promising integrative therapy for DED, acting through key inflammatory pathways. This supports their translational potential in modern ocular therapeutics combining traditional and evidence-based medicine.