Neuro Protective Effect of Baicalein Against Oxaliplatin-Induced Peripheral Neuropathy: Impact on Oxidative Stress, Neuro-inflammation and WNT/β-Catenin Signaling

Abstract Oxaliplatin, an effective anti-cancer agent used in the treatment of colorectal cancer, associated with severe dose limiting side effect peripheral neuropathy, which currently remains a major unmet clinical need. This study was designed to investigate the possible neuroprotective potential of a bioflavonoid, Baicalein in an experimental model of oxaliplatin induced peripheral neuropathy. Rats were administered with a dose of 4 mg/kg oxaliplatin i.p. twice per week for four weeks and they were evaluated for behavioural and functional nerve parameters, followed by bio-chemical, immunohistochemical and western blot analysis. Results from this study show that baicalein reversed oxaliplatin-induced behavioural deficits and significantly prevented oxaliplatin-induced sensory nerve conduction deficits in rats. Molecular analysis revealed baicalein significantly strengthened the antioxidant defense system by enhancing the expression of MnSOD, HO-1 and GSH levels. Baicalein treatment neutralized the oxaliplatin-induced neuroinflammation which was evident from the significant loss of inflammatory mediators like TNF-α, IL-6 and a shunted NF-κB nuclear translocation. Additionally, Baicalein treatment resulted in a significant downregulation of active β-catenin, Wnt5b and Wnt3a proteins. In line with the in vivo evidences, treatment of baicalein in Neuro2a cells showed suppression of oxaliplatin induced ROS, mitochondrial superoxide levels and improved neuritogenesis against oxaliplatin-induced toxicity in Neuro2a cells. Additionally, Baicalein did not alter the cell viability of oxaliplatin in HCT-116 cell line. Collectively, these characteristics suggest that baicalein may be useful in the clinical management of peripheral neuropathy associated with oxaliplatin.