Tetrahydrocurcumin for Major Depressive Disorder with Therapeutic Potential and Mechanistic Insights from Clinical and Preclinical Studies
Abstract
Major depressive disorder (MDD) remains a leading cause of disability worldwide, and while selective serotonin reuptake inhibitors (SSRIs) are standard treatments, they have limited efficacy and adverse effects. Tetrahydrocurcumin (THC), a bioactive metabolite of curcumin, shows anti-inflammatory and neuroprotective properties that may augment antidepressant therapy. This study aimed to evaluate the efficacy and mechanisms of THC in treating MDD. A randomized, open-label, parallel-group pilot trial enrolled 19 patients with major depressive disorder (MDD) who received either escitalopram (ESC, 10 mg/day) or ESC plus tetrahydrocurcumin (ESC + THC, 10 mg ESC + 200 mg THC per day) for 29 days. Participants were randomized 1:1, with blinded raters assessing depressive severity using the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and Day 29. Sixteen participants completed the primary endpoint assessment. Serum underwent data-independent acquisition (DIA-PASEF) proteomics, molecular docking, and ELISA. In parallel, chronic restraint stress (CRS) mice received THC (80 mg/kg) and were evaluated by behavior, immunofluorescence, and serum biomarkers. THC augmentation improved gastrointestinal symptoms in patients (p = 0.025), though total HAMD scores showed no significant group differences. Proteomic analysis identified 32 differentially expressed serum proteins, with THC modulating neurodegenerative pathways. In CRS mice, THC administration reversed anxiety- and…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 19 participants or records.
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