Orexinergic modulation by Uwhangchungsimwon restores homeostasis of GABA/BDNF signaling in insomnia-depression comorbidity
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE
Uwhangchungsimwon (UCW) is a traditional East Asian multi-herbal formulation, used for managing stroke, convulsions, and mental confusion. Given the close association between stress, sleep disturbance, and mood disorders, UCW may hold therapeutic potential for insomnia-depression comorbidity, although its underlying mechanisms remain unclear. This study aims to explore the therapeutic potential of UCW for insomnia-depression comorbidity by targeting the orexinergic and GABAergic systems and identifying its bioactive compounds.
METHODS
In vivo experiments were performed in caffeine (CAF)-induced insomnia models of ICR mice, treated with CAF and UCW for 1 or 6 days. Sleep-wake patterns were monitored with the PiezoSleep system, and depression-like behaviors assessed using the Open Field Test (OFT) and Tail Suspension Test (TST). Hypothalamus and hippocampus from chronically exposed mice were analyzed for biomarker changes. To identify UCW's bioactive compounds, network pharmacology, molecular docking, molecular dynamics, DARTS assay, and calcium influx assay were employed.
RESULTS
UCW (400-800 mg/kg, po) markedly improved sleep-wake patterns, circadian rhythm, and depression-like behaviors in CAF-treated mice. CAF elevated serum corticosterone, hypothalamic orexin A, and OX1R, OX2R, GABABR1, BDNF, TNF-α, IL-6, and IL-1β levels in the hypothalamus and hippocampus, which were all reversed by UCW. In silico, in vitro, and in vivo analyses identified…
Read the paper
Related studies
- Improving the translation of search strategies using the Polyglot Search Translator: a randomized controlled trial
- Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among Older Adults: A Randomized Controlled Trial
- Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study
- A randomized, controlled trial of oral propranolol in infantile hemangioma
- Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study
- Increased physical activity improves sleep and mood outcomes in inactive people with insomnia: a randomized controlled trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.