Neuroprotective and acetylcholinesterase inhibitory activity of plumbagin in ICV-LPS induced behavioral deficits in rats

Abstract

• ICV-LPS treated rats exhibited memory deficits and anxiety-like behavior in rats. • The neuroprotective effect of plumbagin mediated through mitigation of oxidative stress and inflammation. • In-silico study revealed binding affinity of plumbagin on acetylcholinesterase site. • Plumbagin could be considered as promising therapeutic agent in the neuroprotection against behavioral disorders. Plumbagin (5‑hydroxy-2-methyl-1,4-naphthoquinone), a phytoconstituent has been shown to exhibit potent antioxidant and anti-inflammatory effects. In the present investigation, we explored the neuroprotective effects of plumbagin against intracerebroventricular (ICV) lipopolysaccharide (LPS)-induced behavioral deficits. We found that ICV administration of LPS (5 μg/5μl in each ICV injection) bilaterally in the hippocampus caused significant reduction in learning and memory abilities of rats. Moreover, ICV-LPS treated rats displayed anxiety-like behavior evident by open field test and elevated plus maze test. Biochemical analysis in the hippocampus revealed oxidative-nitrosative stress, mitochondrial complexes (I, II, and III) impairment and cholinergic dysfunction in ICV-LPS rats. However, pre- and post-treatment with plumbagin (10 and 20 mg/kg) dose-dependently attenuated ICV-LPS induced oxidative stress (reduction of MDA and nitrite with GSH elevation), mitochondrial impairment, and cholinergic dysfunction (reduction of AChE) in the hippocampus. The pro-inflammatory cytokine (IL-1β) was also found to be increased in the ICV-LPS treated group which was markedly reduced by the treatment of Plumbagin-20 mg/kg. Further, i n-silico analysis revealed that the calculated dock score (-5.116 kcal/mol) and predicted binding energy (-45.800 kcal/mol) supports the binding of plumbagin in the binding site of AChE. All these findings support the neuroprotective effect of plumbagin against ICV-LPS induced behavioral and neurochemical deficits in rats. Thus, plumbagin may be considered an intriguing pharmacological intervention for the management of behavioral dysfunction.