Modulation of IL-1β and TGF-β1 Gene Expression in Stress-Induced Depression Rat Supplemented with Malaysian Acacia Honey

Chronic stress is a key risk factor for depression and metabolic dysfunction, widely mediated through oxidative stress and inflammatory pathways. Natural products such as honey are increasingly investigated for their potential to attenuate stress-induced pathophysiological changes. This study evaluated the protective effects of Malaysian Acacia honey (AH) on glucose regulation, oxidative damage, histopathological alterations, and pro-inflammatory cytokine expression in stress-induced rats. Male Sprague-Dawley rats (n = 42) were subjected to chronic unpredictable mild stress and supplemented with AH, amitriptyline (AMT), or their combination for 28 days. Blood glucose levels, erythrocyte hemolysis, histological changes in liver and kidney, and expression of IL-1β and TGF-β1 in ileum, caecum, and hypothalamus were assessed. Data were reported as mean and standard error of mean (SEM) after three or more independent experiments had been conducted. The data were analyzed using a paired-<i>t</i>-test or a one-way or two-way analysis of variance (ANOVA) and considered significant if <i>p</i> < 0.05. Stress markedly elevated glucose levels (7.97 ± 0.20 mmol/L), increased hemolysis (14.30% ± 2.96), and induced hepatic (cytoplasmic vacuolation, 1.40 ± 0.25; cell lining absent, 1.20 ± 0.37) and renal lesions (dilated intertubular capillaries, 1.40 ± 0.51; inflammation, 2.20 ± 0.20), accompanied by upregulation of <i>IL-1β</i> (1.27-fold ± 0.20) and <i>TGF-β1</i> (1.00-fold ± 0.08). Supplementation with AH significantly reduced hyperglycemia, inhibited hemolysis, ameliorated tissue damage, and downregulated pro-inflammatory cytokines. Combination therapy with AH and AMT produced the most significant improvements near to normal level, suggesting synergistic benefits. These findings highlight the therapeutic potential of AH as a natural adjunct in managing stress-related metabolic and inflammatory disturbances.