Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Oxidative stress-induced retinal ganglion cell (RGC) apoptosis is a common pathological pathway in optic neuropathies. Breviscapine (BVP) possesses antioxidant properties, but its protective effect against RGC apoptosis remains unclear. Objectives: To investigate the antagonistic effect of BVP on tert-butyl hydroperoxide (TBHP)-induced apoptosis in primary rat RGCs and evaluate its dose-dependency. Methods: Primary RGCs from 10 Sprague-Dawley (SD) rats were exposed to TBHP (100 ?mol/L) and treated with BVP (0, 10, 20, 50 ?mol/L). Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Annexin V/propidium iodide (Annexin V/PI) flow cytometry. Protein expression of synaptophysin, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cleaved caspase-3 was measured by Western blotting. Results: BVP treatment significantly increased synaptophysin and Bcl-2 expression, decreased Bax and cleaved caspase-3 expression and reduced the apoptotic rate in a dose-dependent manner (P < 0.05). The apoptotic rates in the blank control, disease control, low-dose, medium-dose and high-dose BVP groups were (2.12 ± 0.73)%, (64.13 ± 10.14)%, (14.13 ± 4.12)%, (10.23 ± 3.03)% and (6.13 ± 3.12)%, respectively. Flow cytometry confirmed that the total apoptotic rate in the high-dose group decreased to (5.79 ± 0.89)%, approaching the level of the blank control group. Conclusion: BVP inhibits TBHP-induced RGC apoptosis in a dose-dependent manner, possibly by regulating the Bcl-2/Bax/caspase-3 pathway. These findings support its potential as a therapeutic candidate for oxidative stress-associated optic neuropathies.