Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, 02447, Republic of Korea.
Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul, 02447, Republic of Korea.
Eur J Pharmacol. 2023 Oct 5;956:175954. doi: 10.1016/j.ejphar.2023.175954. Epub 2023 Aug 2.
Oleanolic acid (OA) and ursolic acid (UA) are structural isomeric triterpenoids. Both triterpenoids have been reported to be able to improve depression. However, no studies have compared their effects in the same system. Whether OA or UA could ameliorate depression-like behaviors in maternal separation (MS)-induced depression-like model was investigated. MS model is a well-accepted mouse model that can reflect the phenotype and pathogenesis of depression. Depression is a mental illness caused by neuroinflammation or changes in neuroplasticity in certain brain regions, such as the prefrontal cortex and hippocampus. Depression-like behaviors were measured using splash test or forced swimming test. In addition, anxiety-like behaviors were also measured using the open field test or elevated plus-maze test. MS-treated female mice showed greater depression-like behaviors than male mice, and that OA improved several depression-like behaviors, whereas UA only relieved anxiety-like behavior of MS-treated mice. Microglial activation, expression levels of TNF-α, and mRNA levels of IDO1 were increased in the hippocampi of MS-treated female mice. However, OA and UA treatments attenuated such increases. In addition, expression levels of synaptophysin and PSD-95 were decreased in the hippocampi of MS-treated female mice. These decreased expression levels of synaptophysin were reversed by both OA and UA treatments, although decreased PSD-95 expression levels were only reversed by OA treatment. Our findings suggest that MS cause depression-like behaviors through female-specific neuroinflammation, changes of tryptophan metabolism, and alterations of synaptic plasticity. Our findings also suggest that OA could reverse MS-induced depression-like behaviors more effectively than UA.
齐墩果酸（OA）和熊果酸（UA）是结构同分异构体的三萜类化合物。这两种三萜类化合物都被报道能够改善抑郁。然而，没有研究比较过它们在同一系统中的效果。本研究旨在探讨 OA 和 UA 是否能够改善母婴分离（MS）诱导的抑郁样模型中的抑郁样行为。MS 模型是一种公认的小鼠模型，能够反映抑郁的表型和发病机制。抑郁是一种由特定脑区（如前额叶皮层和海马体）的神经炎症或神经可塑性改变引起的精神疾病。使用飞溅测试或强迫游泳测试来测量抑郁样行为。此外，还使用旷场试验或高架十字迷宫试验来测量焦虑样行为。MS 处理的雌性小鼠表现出比雄性小鼠更明显的抑郁样行为，而 OA 改善了几种抑郁样行为，而 UA 仅缓解了 MS 处理的雌性小鼠的焦虑样行为。MS 处理的雌性小鼠海马体中的小胶质细胞激活、TNF-α 的表达水平和 IDO1 的 mRNA 水平增加。然而，OA 和 UA 处理可减轻这些增加。此外，MS 处理的雌性小鼠海马体中的突触小体蛋白和 PSD-95 的表达水平降低。OA 和 UA 处理均可逆转突触小体蛋白的这种降低表达水平，尽管 OA 处理仅可逆转 PSD-95 的降低表达水平。我们的研究结果表明，MS 通过雌性特异性神经炎症、色氨酸代谢的变化和突触可塑性的改变引起抑郁样行为。我们的研究结果还表明，OA 逆转 MS 诱导的抑郁样行为的效果比 UA 更有效。
