Effects of Mulberry Juice on Inflammatory Status and Clinical Symptoms in Patients With General Anxiety Disorder
- Conditions
- Systemic InflammationGeneral Anxiety DisordersInterleukin
- Interventions
- Other: Mulberry juice
- Registration Number
- NCT03935061
- Lead Sponsor
- Taipei Medical University
- Brief Summary
Anxiety and depression are normally associated with inflammation reactions and interleukin (IL) related pathways are most evidently involved. IL-17A (interleukin 17A) induces psoriasis-like inflammation and depression-like behaviors in animals and can be relieved by using IL-17A antibody. Also, human association studies found that IL-17A and certain downstream ILs are associated with the severity of anxiety. IL-17A is a sentinel cytokine. On binding with interleukin 17A receptor (IL-17RA) and interleukin 17C receptor (IL-27RC), it induces signaling cascades via nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), P38 mitogen-activated protein kinases (p38MAPK) and CCAAT-enhancer-binding proteins (C/EBPs) knots, and stimulates subsequent cell secretions of cytokines and chemokines. Cyanidin 3-O-glucoside, the main anthocyanin component of mulberry, competes with IL-17A to bind its receptors and inhibits subsequent downstream cascades. The investigators plan to use a single-blinded randomized controlled trial to evaluate the auxiliary effect of mulberry juice in general anxiety disorder, including differences in psychiatric symptoms and levels of IL-related markers between the experimental and control groups, and contribution of IL-related genes in the auxiliary effect.
- Detailed Description
The etiology, pathogenesis, and pathophysiology of psychiatric disorders are not limited to the brain. Anxiety and depression are normally associated with inflammation reactions and interleukin (IL) related pathways are most evidently involved. Previous animal studies showed that administration of IL-17A induces psoriasis-like inflammation and depression-like behavior, and can be relieved by using IL-17A antibody, while in humans, association studies showed that serum IL-17A and certain downstream ILs are associated with the severity of anxiety. Also, the result of human genetic studies also identified several IL genes associated with anxiety and depression. IL-17A is a sentinel cytokine. On binding with interleukin 17A receptor (IL-17RA) and interleukin 17C receptor (IL-27RC), it induces signaling cascades via nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), P38 mitogen-activated protein kinases (p38MAPK) and CCAAT-enhancer-binding proteins (C/EBPs) knots, and stimulates subsequent cell secretions of cytokines and chemokines. Many studies have demonstrated that consumption of proanthocyanidin-rich or anthocyanin-rich berries, berries juice or other secondary products reduce a variety of inflammation symptoms in humans. However, these berries do not meet a low-cost requirement for general nutritional recommendation and new drug development in Taiwan due to the additional import cost. On the other hand, cyanidin 3-O-glucoside, the main anthocyanin component of local mulberry, competes with IL-17A to bind its receptors and inhibits subsequent downstream cascades. Without interfering the on-going treatment of the patients, this proposal plans to use a single-blinded randomized controlled trial to evaluate the auxiliary effect of mulberry juice in general anxiety disorder, including differences in psychiatric symptoms (anxiety, depression, and functions) and levels of IL-related markers between the experimental and control groups, and contribution of IL-related genes in the auxiliary effect.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 104
• meet the criteria for GAD in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, as their primary diagnosis
- severe physical diseases that required intensive care or additional medical attention such as terminal cancer, stroke, and end-stage renal disease
- psychotic symptoms or recent suicide attempts
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mulberry juice Mulberry juice Two bottles (600 ml/bottle) of sanitized mulberry juice are delivered to the patients of the experimental group 20 days before the next clinic visit, with instruction to consume 50 ml of juice diluted with drinking water at room temperature. A reminder of the next clinic visit for continuous treatment is attached.
- Primary Outcome Measures
Name Time Method General Anxiety Disorder-7 items (GAD-7) 5 to 10 minutes GAD-7 measures anxiety status. The questionnaire is self-reported.
Patient Health Questionnaire-9 items (PHQ-9) 5 to 10 minutes PHQ-9 measure depression status. This questionnaire is self-reported.
World Health Organization Quality of Life - Brief (WHOQOL-BREF) 5 to 10 minutes WHOQOL-BREF measures the quality of life. The questionnaire is self-reported.
- Secondary Outcome Measures
Name Time Method Inflammation genes 24 months Inflammation genes including CRP, cytokines (IL-6, IL-1β, TNF-α, G-CSF, GM-CSF, and TGF-β), chemokines (IL-8, GRO-α, and MCP-1), and PGE in addition to IL-17A, are to be genotyped.
Inflammation markers 6 months Inflammation status of the patients are evaluated by measuring CRP, known cytokines (Interleukin- 6 \[IL-6\], Interleukin-1β \[IL-1β\], tumor necrosis factor-α (TNF-α), granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\], and transforming growth factor \[TGF-β\]), chemokines (IL-8, GRO-α, and MCP-1), and PGE in sera, in addition to the sentinel molecule IL-17A. All markers are measured by using ELISA assays according to manufacturer instructions.
Trial Locations
- Locations (1)
Taipei Medical University Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan