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

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 [NF kappa B], 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-alpha], interleukin [IL]-1 beta, 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, NF kappa B, 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-alpha, IL-1 beta, 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.