Journal of ethnopharmacology · 2026
Herb pair of Eucommiae Folium and Gardeniae Fructus enhanced hippocampal PACAP-mediated neuroplasticity via the non-classic downstream PI3K/AKT signaling to exert antidepressant effects.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yin Ying, Wu Zhangjie, Liu Ruiyi, Song Chenghao, Deng Mingxue, Wu Changyu, Lai Shixiong, Tan Jingwen, Fu Zhenzhen, Xing Shan, Wong Nga Lee, Peng Yuhan, Zheng Qiaowei, Liu Yiyao, Huang Zeping, Han Mingzhi, Nam Nguyen Truong, Tan Jun, Huang Zihao, Xie Huijun, Chen Gang
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Conventional antidepressant therapy necessitates prolonged medication, which can result in a plethora of adverse effects, including osteoporosis. Eucommiae Folium (EF) has been demonstrated to alleviate depressive symptoms and osteoporosis. Gardeniae Fructus (GF) also has remarked antidepressant potential, which is often used together with EF as a herb pair in the clinics. This herb pair is highly valuable in synergistically and safely exerting antidepressant effects.
AIM OF THE STUDY: PACAP is a novel antidepressant target, via enhancing neuroplasticity. Here, we aimed to examine the synergistic effects of EF and GF (EG) on depression, and test underlying mechanisms of PACAP and its downstream signaling.
MATERIALS AND METHODS: The antidepressant effects of EG were confirmed in both CUMS and LPS depression models, with fluoxetine as a positive control. Network pharmacology analysis was utilized to reveal the associated mechanisms. The key signaling mechanisms were examined with immunoblotting and immunofluorescence, and further verified by knockdown of PACAP with virus-mediated RNAi.
RESULTS: EG exhibited synergistic efficacy in antidepressant response. EG alleviated depressive and anxiety symptoms in both the CUMS and LPS models, with effects comparable to fluoxetine. Network pharmacology analysis revealed the important role of PI3K/AKT/mTOR signaling pathway, which was verified in the hippocampus following EG treatment. Moreover, the expression of the potential upstream activator, PACAP, was also upregulated, in addition to enhanced the expressions of the synaptic proteins PSD95 and Synapsin-1. EG reduced the number of Iba-1+ microglial cells and their cell areas, and increased the number of BDNF+ cells in the hippocampus. Importantly, hippocampal PACAP knockdown blunted the antidepressant effects of EG and the PI3K/AKT/mTOR signaling.
CONCLUSIONS: The herb pair of Eucommiae Folium and Gardeniae Fructus synergistically elicited antidepressant effects, likely via activating hippocampal PACAP and its downstream PI3K/AKT/mTOR signaling.
AIM OF THE STUDY: PACAP is a novel antidepressant target, via enhancing neuroplasticity. Here, we aimed to examine the synergistic effects of EF and GF (EG) on depression, and test underlying mechanisms of PACAP and its downstream signaling.
MATERIALS AND METHODS: The antidepressant effects of EG were confirmed in both CUMS and LPS depression models, with fluoxetine as a positive control. Network pharmacology analysis was utilized to reveal the associated mechanisms. The key signaling mechanisms were examined with immunoblotting and immunofluorescence, and further verified by knockdown of PACAP with virus-mediated RNAi.
RESULTS: EG exhibited synergistic efficacy in antidepressant response. EG alleviated depressive and anxiety symptoms in both the CUMS and LPS models, with effects comparable to fluoxetine. Network pharmacology analysis revealed the important role of PI3K/AKT/mTOR signaling pathway, which was verified in the hippocampus following EG treatment. Moreover, the expression of the potential upstream activator, PACAP, was also upregulated, in addition to enhanced the expressions of the synaptic proteins PSD95 and Synapsin-1. EG reduced the number of Iba-1+ microglial cells and their cell areas, and increased the number of BDNF+ cells in the hippocampus. Importantly, hippocampal PACAP knockdown blunted the antidepressant effects of EG and the PI3K/AKT/mTOR signaling.
CONCLUSIONS: The herb pair of Eucommiae Folium and Gardeniae Fructus synergistically elicited antidepressant effects, likely via activating hippocampal PACAP and its downstream PI3K/AKT/mTOR signaling.
Предметные рубрики MeSH
AnimalsAntidepressive AgentsHippocampusNeuronal PlasticityProto-Oncogene Proteins c-aktSignal TransductionGardeniaEucommiaceaePituitary Adenylate Cyclase-Activating PolypeptideMaleDepressionTOR Serine-Threonine KinasesPhosphatidylinositol 3-KinasesMicePlant ExtractsDrug SynergismDisks Large Homolog 4 ProteinLipopolysaccharidesFluoxetineDisease Models, AnimalFruit