Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana.
Department of Pharmaceutics and Microbiology, School of Pharmacy, College of Health Sciences, University of Ghana, Accra, Ghana.
Neuroscience. 2024 Nov 12;560:90-105. doi: 10.1016/j.neuroscience.2024.09.024. Epub 2024 Sep 21.
The gut microbiota has been posited as a target for the treatment of major depressive disorder. Herein, we investigated the effect of the hydroethanolic leaf extract of Mallotus oppositifolius (MOE) on the gut microbiota of mice and how this contributes to its known antidepressant-like effect. A 6-week chronic unpredictable mild stress (CUMS) procedure was employed in 7 groups of mice to induce depression. From the third week, oral MOE treatments (10, 30, 100 mg/kg) and two reference drugs, fluoxetine (12 mg/kg) and minocycline (40 mg/kg), known to affect the gut microbiota, were administered. The sixth and seventh groups were the vehicle stressed (VEH-S) and non-stressed groups (VEH-NS). Changes in depressive-like behaviors were assessed using sucrose preference test while the forced swimming test (FST) was used to assess sustained antidepressant-effect after treatment discontinuation. Moreover, changes in prefrontal cortex (PFC) and hippocampal serotonin (5-HT) levels were evaluated using enzyme-linked immunosorbent assay (ELISA). The effect of treatment on the profile of the gut microbiota of the groups was elucidated using 16S rRNA Oxford Nanopore sequencing. MOE and reference drugs reversed the depression-associated reduction in sucrose preference when compared to VEH-S. MOE (with peak effect at 30 mg/kg) reduced immobility while increasing swimming and climbing behaviors. MOE reversed CUMS-induced reduction of 5-HT concentration in PFC and hippocampus. The behavioral effects of MOE were associated with shifts in the gut microbiota of CUMS-exposed mice. The study has provided seminal evidence that MOE ameliorates CUMS-induced depressive symptoms by modulating gut microbiota and increasing brain 5-HT levels.
肠道微生物群被认为是治疗重度抑郁症的一个靶点。在此，我们研究了 Mallotus oppositifolius（MOE）水醇提叶提取物对小鼠肠道微生物群的影响，以及这如何有助于其已知的抗抑郁作用。采用 6 周慢性不可预测轻度应激（CUMS）程序对 7 组小鼠进行处理，以诱导抑郁。从第 3 周开始，对小鼠进行口服 MOE 治疗（10、30、100mg/kg）和两种对照药物氟西汀（12mg/kg）和米诺环素（40mg/kg）的治疗，这两种药物已知会影响肠道微生物群。第六组和第七组为载体应激（VEH-S）和非应激组（VEH-NS）。使用蔗糖偏好测试评估抑郁样行为的变化，使用强迫游泳测试（FST）评估治疗停止后持续的抗抑郁作用。此外，使用酶联免疫吸附测定（ELISA）评估前额叶皮层（PFC）和海马 5-羟色胺（5-HT）水平的变化。使用 16S rRNA Oxford Nanopore 测序阐明治疗对各组肠道微生物群特征的影响。与 VEH-S 相比，MOE 和对照药物逆转了与抑郁相关的蔗糖偏好降低。MOE（在 30mg/kg 时效果最佳）减少了不动性，同时增加了游泳和攀爬行为。MOE 逆转了 CUMS 引起的 PFC 和海马 5-HT 浓度降低。MOE 的行为效应与暴露于 CUMS 的小鼠肠道微生物群的变化有关。该研究提供了开创性的证据，表明 MOE 通过调节肠道微生物群和增加大脑 5-HT 水平来改善 CUMS 引起的抑郁症状。
