Areca Thirteen Pill Improves Depression in Rat by Modulation of the Chemokine/Chemokine Receptor Axis.

Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1ß were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.

The long-term effect of modulated acoustic stimulation on alteration in EEG brain network of chronic tinnitus patients: An exploratory study.

Acoustic stimulation is one of the most influential techniques for distressing tinnitus, while how it functions to reverse neural changes associated with tinnitus remains undisclosed. In this study, our objective is to investigate alterations in brain networks to shed light on the enigma of acoustic intervention for tinnitus. We designed a 75-day long-term acoustic intervention experiment, during which chronic tinnitus patients received daily modulated acoustic stimulation with each session lasting 15 days. Every 15 days, professional tinnitus assessments were conducted, collecting both electroencephalogram (EEG) and tinnitus handicap inventory (THI) data from the patients. Thereafter, we investigated the changes in EEG network organizations during continuous acoustic stimulation and their progressive evolution throughout long-term therapy, alongside exploring the associations between the evolving changes of the network alterations and THI. Our current study findings reveal reorganization in alpha/beta long-range frontal-parietal-occipital connections as well as local frontal and parietal-occipital regions induced by acoustic stimulation. Furthermore, we observed a decrease in modulation effects as therapy sessions progressed. These alterations in brain networks reflect the reversal of tinnitus-related neural activities, particularly distress and perception; thus contributing to tinnitus rehabilitation through long-term modulation effects. This study provides unique insights into how long-term acoustic intervention affects the network organizations of tinnitus patients and deepens our understanding of the pathophysiological mechanisms underlying tinnitus rehabilitation.

Correlation Analysis of EEG Brain Network With Modulated Acoustic Stimulation for Chronic Tinnitus Patients.

The acoustic stimulation influences of the brain is still unveiled, especially from the brain network point, which can reveal how interaction is propagated and integrated between different brain zones for chronic tinnitus patients. We specifically designed a paradigm to record the electroencephalograms (EEGs) for tinnitus patients when they were treated with consecutive acoustic stimulation neuromodulation therapy for up to 75 days, using the tinnitus handicap inventory (THI) to evaluate the tinnitus severity or the acoustic stimulation treatment efficacy, and the EEG to record the brain activities every 2 weeks. Then, we used an EEG-based coherence analysis to investigate if the changes in brain network consistent with the clinical outcomes can be observed during 75-days acoustic treatment. Finally, correlation analysis was conducted to study potential relationships between network properties and tinnitus handicap inventory score change. The EEG network became significantly weaker after long-term periodic acoustic stimulation treatment, and tinnitus handicap inventory score changes or the acoustic stimulation treatment efficacy are strongly correlated with the varying brain network properties. Long-term acoustic stimulation neuromodulation intervention can improve the rehabilitation of chronic tinnitus patients, and the EEG network provides a relatively reliable and quantitative analysis approach for objective evaluation of tinnitus clinical diagnosis and treatment.