Background: Dendrobium spp. has traditionally been used to improve visual function, and related formulations, such as Dendrobium Glow in dark pills, are currently used in the management of dry eye disease (DED). This study investigated the positive effects and underlying mechanisms of 3-O-methylgigantol, an active compound from Dendrobium spp., against DED using network pharmacology and in vitro experimental validation. Methods: Active compounds and targets were identified through database screening, and network analysis was used to identify the key compounds and targets. Molecular docking and dynamic simulations were performed to verify the binding of 3-O-methylgigantol to the epidermal growth factor receptor (EGFR). An in vitro DED model was established using hyperosmotic sodium chloride (550 mOsm) in human corneal epithelial cells (HCECs). The effects of 3-O-methylgigantol, with or without the EGFR inhibitor (erlotinib), on cell viability, apoptosis, reactive oxygen species, and inflammatory cytokines were assessed. Results: Network pharmacology predicted 3-O-methylgigantol as a key active compound and EGFR as a core target. Molecular simulations confirmed stable binding. In vitro experiments showed that 3-O-methylgigantol significantly increased HCEC viability and reduced apoptosis, reactive oxygen species accumulation, and inflammatory cytokine release under hyperosmotic conditions. The EGFR inhibitor erlotinib attenuated these protective effects. Conclusions: 3-O-methylgigantol, an active compound from Dendrobium spp., alleviates hyperosmolarity-induced corneal epithelial cell damage, oxidative stress, and inflammation by activating the EGFR signaling pathway. This compound may represent a potential therapeutic candidate for DED management, demonstrating its efficacy in restoring tear film homeostasis in in vitro models.
Zhu et al. (Wed,) studied this question.