Neuroprotective Effects of a Novel Polyherbal Formulation Against Cyclophosphamide-Induced Cytotoxicity in SH-SY5Y Cells.

Cyclophosphamide (CP) is an anticancer drug, but its long-term use is commonly associated with neurotoxicity. We investigated the neuroprotective effects of a novel polyherbal formulation (PHF) on CP-induced neurotoxicity in SH-SY5Y cells and its mechanism of action. PHF showed strong antioxidant action and mitigated CP-induced SH-SY5Y toxicity by significantly (p < 0.05-0.001) increasing the cell viability by 51.44%, 71.28%, and 98.43% at doses 250, 500, and 1000 µg/mL, respectively. CP-induced oxidative stress in SH-SY5Y cells was associated with a significant (p < 0.001) decline in DPPH (by 40.26%), ABTS (by 44.98%), and CUPRIC (by 68.95%) activities. Interestingly, PHF prevented lipid peroxidation, ROS and apoptosis, and enhanced MMP level and the antioxidant status in SH-SY5Y cells. The phytocompounds detected in PHF showed strong binding affinity with CP-activator enzymes (CYP2D6 and CYP2C19) and oxidative stress-related markers (AChE and GST), which support the in vitro findings. PHF could be useful in the prevention/treatment of chemotherapy-associated neurodegenerative disorders.