helicide and Disease-Models--Animal

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-1β, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKβ, p-IкBα, p-IKKβ, NF-кB p65, and IкBα 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-1β, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKβ in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKβ, and NF-κB 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/IκBα/NF-κB pathway.

Topics: Animals; Antidepressive Agents; Benzaldehydes; Depression; Disease Models, Animal; I-kappa B Kinase; Male; NF-kappa B; Rats, Sprague-Dawley; Signal Transduction; Stress, Psychological

Helicid (4-formylphenyl-β-D-allopyranoside) is a bioactive constituent of Helicid nilgirica Bedd that has been used in Chinese traditional herbal medicine to treat headache, insomnia, and depression. However, the underlying mechanisms of these effects are unclear. We have now investigated the effect of helicid on depression-related behaviors in rats exposed to chronic unpredictable mild stress (CUMS) and have also explored possible underlying mechanisms that involve neurotrophin expression. After 6 weeks isolation, body weight and sucrose preference were significantly reduced in rats with CUMS-induced depression compared with controls. The CUMS rats also showed significant inhibition of locomotory parameters in open field tests (involving behavioral assays). Helicid significantly regulated levels of corticosterone (CORT), inflammatory cytokines and 5-hydroxytryptamine (5-HT). Helicid also reversed CUMS-induced decreases of 5-HT1A receptor expression and promoted brain derived neurotrophic factor (BDNF) expression in the hippocampus The significant reversal of depressive-like behaviors by helicid is similar to that achieved by fluoxetine. The antidepressive effects are likely attributable to the promotion of hippocampal neurotrophin expression through activation of the serotonergic system. Helicid thus has potential for treating depressive disorders.

Topics: Animals; Antidepressive Agents; Benzaldehydes; Brain-Derived Neurotrophic Factor; Corticosterone; Depression; Disease Models, Animal; Hippocampus; Humans; Male; Medicine, Chinese Traditional; Motor Activity; Nerve Growth Factors; Proteaceae; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Serotonin

Natural helicid (4-formylphenyl-O-β-d-allopyranoside), a main active constituent from seeds of the Chinese herb Helicia nilagirica, has been reported to exert a sedative, analgesic and hypnotic effect, and is used clinically to treat neurasthenic syndrome, vascular headaches and trigeminal neuralgia. In the current study, mechanical allodynia tests, electroencephalograms, electromyogram recordings and c-Fos expression in neuropathic pain-like model mice of partial sciatic nerve ligation were used to investigate the effect of helicid on neuropathic pain and co-morbid insomnia. Our results showed that helicid at a dose of 100, 200 or 400 mg kg

Topics: Analgesics; Animals; Benzaldehydes; Disease Models, Animal; Electroencephalography; Electromyography; Genes, fos; Gyrus Cinguli; Hyperalgesia; Hypnotics and Sedatives; Hypothalamic Area, Lateral; Ligation; Male; Mice; Neuralgia; Preoptic Area; Sciatic Nerve; Sleep; Sleep Initiation and Maintenance Disorders