Depression is a neuropsychiatric disease that significantly impacts the physical and mental health of >300 million people worldwide and places a major burden on society. Ginsenosides are the main active ingredient in ginseng and have been proven to have various pharmacological effects on the nervous system. Herein, we investigated the antidepressant effect of ginsenoside Rk3 and its underlying mechanism in a murine model of depression. Rk3 significantly improved depression-like behavior in mice, ameliorated the disturbance of the hypothalamus–pituitary–adrenal axis, and alleviated neuronal damage in the hippocampus and prefrontal cortex of mice. Additionally, Rk3 improved the abnormal metabolism of tryptophan in brain tissue by targeting tryptophan hydroxylase, thereby reducing neuronal apoptosis and synaptic structural damage in the mouse hippocampus and prefrontal cortex. Furthermore, Rk3 reshaped the composition of the gut microbiota of mice and regulated intestinal tryptophan metabolism, which alleviated intestinal barrier damage. Thus, this study provides valuable insights into the role of Rk3 in the tryptophan metabolic cycle along the brain–gut axis, suggesting that Rk3 may have the potential for treating depression.

中文翻译：

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人参皂苷 Rk3 通过靶向色氨酸羟化酶和重塑肠道微环境来调节脑肠轴上的色氨酸代谢，以减轻小鼠的抑郁样行为

抑郁症是一种神经精神疾病，严重影响全球超过3亿人的身心健康，给社会带来重大负担。人参皂苷是人参中的主要活性成分，已被证明对神经系统具有多种药理作用。在此，我们研究了人参皂苷 Rk3 在小鼠抑郁模型中的抗抑郁作用及其潜在机制。 Rk3显着改善小鼠的抑郁样行为，改善下丘脑-垂体-肾上腺轴的紊乱，减轻小鼠海马和前额皮质的神经元损伤。此外，Rk3通过靶向色氨酸羟化酶改善脑组织中色氨酸的异常代谢，从而减少小鼠海马和前额皮质的神经元凋亡和突触结构损伤。此外，Rk3重塑了小鼠肠道微生物群的组成，调节肠道色氨酸代谢，从而减轻肠道屏障损伤。因此，这项研究为 Rk3 在脑肠轴色氨酸代谢循环中的作用提供了有价值的见解，表明 Rk3 可能具有治疗抑郁症的潜力。