Zanthoxylum alatum ameliorates scopolamine-induced amnesia in rats: Behavioral, biochemical, and molecular evidence

Abstract

OBJECTIVE:Hydroethanolic extract of Zanthoxylum alatum seeds (HEZA) in scopolamine-induced amnesia was investigated for memory enhancing activity.MATERIALS AND METHODS:Radial arm maze (RAM) test was performed to evaluate the behavioral activity. Rats were treated with HEZA (50, 100, and 200 mg/kg, p. o.) and tacrine (3 mg/kg. i. p.) for 14 days. Scopolamine (0.4 mg/kg) was injected i. p. into rats after 45 min of drug administration on the 14th day. The messenger RNA (mRNA)/protein profile of few markers (acetylcholinesterase [AChE], heme oxygenase-1 [HO-1], nuclear factor-kappa B [NFκB], nuclear factor erythroid 2–related factor 2 [Nrf2], protein phosphatase 2A[PP2A], Tau, brain-derived neurotrophic factor [BDNF], tropomyosin-related kinase B [TrkB], Bcl-2-associated X protein [Bax], and Caspase-3) were also measured by polymerase chain reaction (PCR) and immunoblotting assay. Brain cytokines (tumor necrosis factor alpha [TNF-α], interleukin [IL]-1 β, and IL-10) in hippocampus were evaluated using commercially available enzyme-linked immunosorbent assay kits.RESULTS:HEZA exhibited anti-amnesic activity as indicated by a significant reduction in the working memory error and reference memory error in RAM. Pretreatment with HEZA significantly down-regulated the expression of AChE, NFκB, Tau, Bax, and Caspase-3 with simultaneous up-regulation of Nrf2, HO-1, PP2A, BDNF, and TrkB genes in the hippocampal tissues similar to tacrine when compared with scopolamine-treated rats. Pretreatment with HEZA attenuated scopolamine-induced elevation of TNF-α, IL-1 β, levels in hippocampus and reversed diminished IL-10 concentrations towards normal levels in the brain.CONCLUSION:Zanthoxylum alatum seeds could probably counteract amnesia. Since its use is mainly reported as a stimulant and tonic, this novel activity could be a boon for the scientists to explore more in this direction.