Corydalis saxicola Bunting total alkaloids trigger apoptosis in oral leukoplakia cells by modulating the Bax/Bcl-2/Caspase-3 signaling axis

Ethnopharmacological relevance: Corydalis saxicola Bunting (CSB) is traditionally used in Traditional Chinese Medicine (TCM) for heat-clearing and treating oral erosion. While its total Alkaloids (CSBTA) show potential against oral diseases, their specific effects and mechanisms in oral leukoplakia (OLK) remain poorly understood.

Aim of the study: To investigate the therapeutic potential and molecular mechanisms of CSBTA in OLK.

Materials and methods: Bioactive components and targets were predicted via network pharmacology and molecular docking. In vitro validation was conducted in Leuk-1 cells using CCK-8, EdU, wound-healing, and flow cytometry assays. Mitochondrial membrane potential and expression of Bax, Bcl-2, Caspase-8, and Cleaved Caspase-3 were analyzed to delineate the mechanistic cascade.

Results: Computational analysis identified 74 active components and 21 core targets predominantly enriched in mitochondrial-mediated programmed cell death. In vitro assays demonstrated that CSBTA significantly inhibited Leuk-1 cells proliferation and migration in a dose-dependent manner. Mechanistic studies revealed that CSBTA induced mitochondrial depolarization and robust Apoptosis. Western blot demonstrated a significant increase in the Bax/Bcl-2 ratio, accompanied by Caspase-8 up-regulation and enhanced Caspase-3 cleavage. Furthermore, the inhibitor Z-VAD-FMK significantly rescued cell viability, confirming that CSBTA-induced death is primarily mediated through the caspase-dependent mitochondrial apoptotic pathway.

Conclusions: CSBTA inhibits OLK progression in vitro by triggering Apoptosis via the Bax/Bcl-2/Caspase-3 axis and the subsequent Caspase cascade. This study provides a solid mechanistic foundation supporting CSBTA as a promising candidate for the clinical management of OLK.