Pharmacological Potentiality of Bioactive Flavonoid against Ketamine Induced Cell Death of PC 12 Cell Lines: An In Vitro Study

Abstract

During the past few years, there has been exponential growth in the field of ethnopharmacology in the treatment of different human ailments, including neurological disorders. In our previous study, we isolated, characterized, and reported a novel bioactive compound with therapeutic efficacy in vivo, which was used in the current study. This study was designed to investigate the pharmacological effect and therapeutic mechanism of the natural plant compound 3-(3,4-dimethoxy phenyl)-1-(4-methoxy phenyl)prop-2-en-1-one against ketamine-induced toxicity in PC 12 cell lines. Cell death was induced in PC 12 cell lines by incubating with ketamine, and the protection offered by the compound at different concentrations was studied during pretreatment. The therapeutic efficacy was screened through MTT assay, LDH assay, DCF-DA assay, clonogenic assay, RT-PCR, and densitometric analysis. The bioactive compound caused a significant elevation in cell viability up to approximately 80%, down-regulation of cell damage, reduction in free radical damage caused by intracellular reactive oxygen species, and up-regulation of cell survival ability, which was dysregulated during ketamine induction. In addition, RT-PCR analysis of DOPA-related genes suggests that the compound exerted significant inhibition in the expression of these genes, which were overexpressed during ketamine induction. The current findings provide new insight into the neuroprotective mediation of bioactive factors as a prospective therapy for neurological disorders.