Triterpenoid from Antrodia cinnamomea Ameliorates Reserpine-Induced Depressive-Like Behaviors and Gut Microbiota Imbalance in Mice

This study aimed to investigate the effects of triterpenoids from Antrodia cinnamomea (ACTp) on reserpine-induced depressive-like symptoms in mice. First, to create a mouse model of depression, injection of reserpine at 0.4 mg/kg m_b (body mass) was selected based on typical depressive symptoms and moderately severe depression. Subsequently, the ameliorative effects of different doses of ACTp on depressive symptoms in mice were studied. It was shown that medium-dose (20 mg/kg m_b) ACTp increased the sugar preference value of depressed mice from 46% to 75% (the value for normal mice is 77%), and alleviated anhedonia. Besides, the medium dose of ACTp increased the horizontal activity of depressed mice by 375% and reduced the immobility time in the tail suspension time by 32% compared with the model group. Its effect was somewhat more pronounced than that of the positive drug fluoxetine. In addition, the medium dose of ACTp significantly reduced the levels of inflammatory factors of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and significantly increased the levels of the neurotransmitters dopamine and serotonin in depressed mice, being comparably effective as fluoxetine. Finally, the effect of ACTp on the gut microbiota of mice was investigated. It was found that the medium dose of ACTp significantly increased the relative abundance of beneficial microorganisms (such as Firmicutes and Ligilactobacillus) in mice. These microorganisms were known to ameliorate depressive symptoms by inhibiting inflammatory cytokines or increasing neurotransmitter levels. The result preliminarily suggests that ACTp may alleviate depressive symptoms in mice through the microbiota-gut-brain axis.