Pharmacological and neuroprotective effects of Helicid alleviates neuronal apoptosis of rats with depression-like behaviors by downregulating lncRNA-NONRATT030918.2

Abstract

Abstract Background Nowadays, evidence demonstrates that inflammation plays an important role in depression. Therefore, new antidepressants may be identified by screening for their anti-inflammatory properties. In parallel, Helicid (HEL) has been found to possess antidepressant pharmacological activity. Therefore, we aimed to testify the precise molecular mechanism by which HEL regulates lncRNA-NONRATT030918.2 to exert its antidepressant effect and pharmacological interventions in depression models.Methods A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a Fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot.Results The HEL can alleviate the depression-like behavior of CUMS rats and reduce the mortality of hippocampal via down-regulating the level of NONRATT030918.2. In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1, as well as increased expression of miRNA-128-3p. This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p, which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1.Conclusions The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects.