Wang Yanping, Jia Yanjun, Zhao Wanning, Shao Yazhou, Zhang Zeyu, Chen Huiru, Qian Shuangxi, Hu Fangdi
School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
School of Pharmacy, Lanzhou University, Lanzhou, China.
Front Pharmacol. 2025 Sep 8;16:1642515. doi: 10.3389/fphar.2025.1642515. eCollection 2025.
Depression is closely associated with dysfunction of the microbiota-gut-brain axis (MGBA). Total phenol from leaves (HLTP) exhibits antidepressant potential, but its role in relieving depression by regulating MGBA remains uninvestigated.
In this study, the chronic unpredictable mild stress (CUMS) method was used to establish a rat model of depression to investigate the ameliorative effects of HLTP on depression.
Behavioral and pathological results showed HLTP improved weight loss, increased sucrose preference, reduced forced swimming immobility time, novel-suppressed feeding latency, open field movement trajectory, and alleviated hippocampal CA1 neuronal damage in CUMS-depressed rats. At 10, 20, and 40 mg/kg, HLTP increased dopamine (DA), noradrenaline (NE), 5-hydroxytryptamine (5-HT), interleukin-10 (IL-10), brain-derived neurotrophic factor (BDNF), and cAMP response element-binding protein (CREB) in the brain. It also decreased the inflammatory factor (TNF-α and IL-1β) in the brain, as well as corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in serum and brain. HLTP modulated gut microbiota diversity and reversed CUMS-induced alterations in 15 bacterial taxa, including and . Additionally, HLTP reversed 63 CUMS-induced abnormal serum metabolites, primarily affecting tryptophan metabolism, niacin and nicotinamide metabolism, and porphyrin metabolism. Significant correlations were observed among gut microbial composition, serum metabolite levels, biochemical indices, and behavioral outcomes.
HLTP exerts antidepressant effects in CUMS-induced rats by modulating the MGBA. It enhances metabolic function, reduces neuroinflammatory damage, restores neurotrophic factor levels, suppresses hyperactivity of the hypothalamic-pituitary-adrenal axis, and corrects monoamine neurotransmitter deficiencies, collectively contributing to the attenuation of depression-related symptoms.
抑郁症与微生物群-肠-脑轴（MGBA）功能障碍密切相关。树叶总酚（HLTP）具有抗抑郁潜力，但其通过调节MGBA缓解抑郁症的作用尚未得到研究。
在本研究中，采用慢性不可预测轻度应激（CUMS）方法建立大鼠抑郁症模型，以研究HLTP对抑郁症的改善作用。
行为和病理结果显示，HLTP改善了体重减轻，增加了蔗糖偏好，减少了强迫游泳不动时间、新奇抑制摄食潜伏期、旷场运动轨迹，并减轻了CUMS诱导的抑郁症大鼠海马CA1神经元损伤。在10、20和40mg/kg剂量下，HLTP增加了大脑中的多巴胺（DA）、去甲肾上腺素（NE）、5-羟色胺（5-HT）、白细胞介素-10（IL-10）、脑源性神经营养因子（BDNF）和环磷酸腺苷反应元件结合蛋白（CREB）。它还降低了大脑中的炎症因子（TNF-α和IL-1β），以及血清和大脑中的促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）和皮质酮（CORT）。HLTP调节肠道微生物群多样性，并逆转了CUMS诱导的15种细菌类群的改变，包括和。此外，HLTP逆转了63种CUMS诱导的异常血清代谢物，主要影响色氨酸代谢、烟酸和烟酰胺代谢以及卟啉代谢。在肠道微生物组成、血清代谢物水平、生化指标和行为结果之间观察到显著相关性。
HLTP通过调节MGBA对CUMS诱导的大鼠发挥抗抑郁作用。它增强代谢功能，减少神经炎症损伤，恢复神经营养因子水平，抑制下丘脑-垂体-肾上腺轴的亢进，并纠正单胺类神经递质缺乏，共同导致抑郁相关症状的减轻。
