Investigating the Effects of Crocin and Hydroalcoholic Extract of Terminalia Chebula on Memory and the Expression of PSD 95, Synapsin-1, and Synaptophysin Genes in the Hippocampus Following Stress in Male Rats

Stress is a stimulus that leads to a physical or psychological reaction. Stress affects memory and cognition. Common drugs for treating stress and memory disorders have limited effects and many side effects, so the search for new effective compounds with natural origin and fewer side effects is of interest. Various studies have shown that Terminalia chebula) T. chebula (and crocin are effective in improving memory. Several proteins, including synapsin-1, synaptophysin, and PSD95, are involved in the transmission of nerve messages in synapses involved in memory. In this study, the effect of the hydroalcoholic extract of T. chebula and crocin in improving memory and stress and the expression of synaptophysin, PSD 95, and synapsin-1 genes in the hippocampal tissue of male rats of the immobility stress model has been evaluated.

25 adult male Wistar rats were randomly divided into five groups, including a control group, a stress group, treated with hydroalcoholic extract of T. chebula group, treated with crocin group, simultaneously treated with hydroalcoholic extract of T. chebula, and crocin group. All groups except the control group were subjected to immobility stress for 14 days.  Crocin was injected intraperitoneally (30 mg/kg) and hydroalcoholic extract of T. chebula was given as intragastric gavage (50 mg/kg). After fourteen days, the shuttle box test was performed to check the memory, then the animals were anesthetized and their hippocampal tissue was isolated, and the expression changes of synapsin-1, synaptophysin, and PSD 95 genes in the tissue were analyzed by Real-time PCR method.

Immobility stress caused disruption in two memory indicators, i.e. increased the duration of staying in the dark chamber (P˂0.01) and decreased the latency time to enter the dark chamber compared to the control group (P˂0.0001). Treatment with the alcoholic extract of T. chebula did not affect the duration of staying in the dark chamber (P>0.05), but crocin decreased it compared to the stress group (P˂0.05). The hydroalcoholic extract of T. chebula and crocin increased the latency time to enter the dark chamber compared to the stress group (P˂0.01 and P˂0.001, respectively). As a result, both of them affected memory improvement parameters. The combination of the hydroalcoholic extract of T. chebula and crocin decreased the duration of staying in the dark chamber (P˂0.05) and increased the latency time to enter the dark chamber compared to the stress group (P˂0.001). Also, Immobility stress decreased the expression of synaptophysin, synapsin-1, and PSD95 genes in the hippocampus tissue compared to the control group (P˂0.001 for all genes). The expression of synaptophysin, synapsin-1, and PSD95 genes in the hippocampus tissue of groups treated with hydroalcoholic extract of T. chebula (P˂0.01, P˂0.01 and P˂0.001, respectively), crocin (P˂0.001, P˂0.01 and P˂0.001, respectively), and their combination (P˂0.001, P˂0.001 and P˂0.01, respectively), increased compared to the stress group.

treatment with crocin and hydroalcoholic extract of T. chebula separately or their combination was effective in improving memory and reducing stress by increasing the expression of synapsin 1, synaptophysin, and PSD95 genes.