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

Chintha Venkataramaiah,Jangampalli Adi Pradeepkiran,Sholapuri Payani,Bandila Lakshmi Priya

doi:10.3390/antiox10060934

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.

Highlights

Numerous neuroprotective screening studies have been conducted using traditional medicinal plants in an attempt to discover new therapeutic agents that are devoid of the toxic side effects generally known to be associated with current therapeutic agents
Prior to the evaluation of the neuroprotective property of the bioactive compound, the median nontoxic concentration (MNTC) and cytotoxic concentration (CC50) of the plant compound and clozapine were determined by incubating PC 12 cell lines with different concentrations of plant compound and clozapine ranging from 20 to 600 μg/mL
The clonogenic assay in the present study indicated a reduction of colony formation capacity in PC 12 cell lines treated with various concentrations of ketamine compared with the control group

Summary

Introduction

Numerous neuroprotective screening studies have been conducted using traditional medicinal plants in an attempt to discover new therapeutic agents that are devoid of the toxic side effects generally known to be associated with current therapeutic agents. Among the active phytoconstituents of plant origin, flavonoids are one the best-studied groups of compounds for their neuroprotective effects, and a selected few are presented here as classical examples of their representative structural class. Li et al (2012) demonstrated the neuroprotective property of the compound baicalein, isolated from Scutellaria baicalensis (Labiatae), against 6-OHD-A-induced. Puerarin is a subclass of flavonoid compounds obtained from Pueraria lobata and was noted for upregulation of phosphorylation of Akt in MPP+ -induced cytotoxicity in SH-SY5Y cells [7]; inhibition of

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Conclusion