Restoring Impaired Neurogenesis and Alleviating Oxidative Stress by Cyanidin against Bisphenol A-induced Neurotoxicity: In Vivo and In Vitro Evidence

Abstract

Background: Bisphenol A (BPA) is a known neurotoxic compound with potentially harmful effects on the nervous system. Cyanidin (CYN) has shown promise as a neuroprotective agent.

Objective: The current study aims to determine the efficacy of CYN against BPA-induced neuropathology.

Methods: In vitro experiments utilized PC12 cells were pre-treated with gradient doses of CYN and further stimulated with 10ng/ml of BPA. DPPH radical scavenging activity, catalase activity, total ROS activity, and nitric oxide radical scavenging activity were done. In vivo assessments employed doublecortin immunohistochemistry of the brain in BPA-exposed Sprague-Dawley rats. Further, In silico molecular docking of CYN with all proteins involved in canonical Wnt signaling was performed using the Autodock v4.2 tool and BIOVIA Discovery Studio Visualizer.

Results: IC₅₀ values of CYN and ascorbic acid were determined using dose-response curves, and it was found to be 24.68 ± 0.563 μg/ml and 20.69 ± 1.591μg/ml, respectively. BPA-stimulated cells pre-treated with CYN showed comparable catalase activity with cells pre-treated with ascorbic acid (p = 0.0287). The reactive species production by CYN-treated cells was significantly decreased compared to BPA-stimulated cells (p <0.0001). Moreover, CYN significantly inhibited nitric oxide production compared to BPA stimulated and the control cells (p < 0.0001). In vivo CYN positively affected immature neuron quantity, correlating with dosage. During molecular docking analysis, CYN exhibited a binding affinity > -7 Kcal/mol with all the key proteins associated with the Wnt/β- catenin signaling cascade.

Conclusion: Conclusively, our finding suggests that CYN exhibited promise in counteracting BPAinduced oxidative stress, improving compromised neurogenesis in hippocampal and cortical regions, and displaying notable interactions with Wnt signaling proteins. Thereby, CYN could render its neuroprotective potential against BPA-induced neuropathology.

Keywords: Neurotoxicity; Wnt; anthocyanin; antioxidant; bisphenol A; cyanidin; neurodegeneration.; neurogenesis.