Antidepressant-like effects of helicid on a chronic unpredictable mild stress-induced depression rat model: Inhibiting the IKK/IκBα/NF-κB pathway through NCALD to reduce inflammation

We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1?, COX-2, and TNF-? levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKK?, p-I?B?, p-IKK?, NF-?B p65, and I?B? were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1?, COX 2, IL-6, TNF-?, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-I?B? and p-IKK? in the cytoplasm and the expression of nuclear NF-?B p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of I?B?, IKK?, and NF-?B p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/I?B?/NF-?B pathway.

Automated summary

The study found that helicid can alleviate depressive-like behaviors in rats exposed to CUMS through the mediation of the NCALD gene, demonstrating its antidepressant effects through various biochemical markers and highlighting its mechanism of regulating neuro-inflammation and the NF-κB pathway.