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马钱苷改善慢性不可预测轻度应激诱导的抑郁样行为和神经化学功能障碍。

Loganin improves chronic unpredictable mild stress-induced depressive-like behaviors and neurochemical dysfunction.

作者信息

Guo Yu-Xuan, Xia Cong-Yuan, Yan Yu, Han Yan, Shi Rui, He Jun, Wang Yu-Ming, Wang Ze-Xing, Zhang Wei-Ku, Xu Jie-Kun

机构信息

School of Life Sciences & School of Chinese Medicine Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China; Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.

Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.

出版信息

J Ethnopharmacol. 2023 May 23;308:116288. doi: 10.1016/j.jep.2023.116288. Epub 2023 Feb 19.

DOI:10.1016/j.jep.2023.116288
PMID:36809822
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Cornus officinalis Sieb. et Zucc., is a valuable herb commonly used in Chinese medicine clinics. Loganin is a major iridoid glycoside obtained from the traditional Chinese herb Corni Fructus. Loganin, which has been shown to improve depression-like behavior in mice exposed to acute stress, is probably a potential antidepressant candidate.

AIM OF THE STUDY

Loganin was evaluated for its effect on chronic unpredictable mild stress (CUMS) induced depressive-like mice, and its action mechanisms were explored.

MATERIALS AND METHODS

ICR mice were subjected to the CUMS stimulation method to induce depression. The therapeutic effect of loganin on depressive-like behavior was evaluated by a series of behavioral tests such as sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST) and open-field test (OFT). In addition, the serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured using western blot analysis.

RESULTS

The results showed that CUMS induced depressive-like behaviors in mice, as indicated by behavioral tests. Administration of loganin increased the sucrose preference in SPT, as well as decreased the immobility time in FST and TST. Loganin could also improve food intake, and increased crossing times in the OFT. In mechanism, loganin restored the secretion of monoamine neurotransmitters, ACTH and CORT to normal levels. In addition, loganin elevated the expression of BDNF in the hippocampus. In conclusion, loganin exerts antidepressant-like effects in CUMS model mice through modulating monoamine neurotransmitters, ACTH, CORT and BDNF.

CONCLUSION

Loganin effectively ameliorated depressive-like symptoms in CUMS-exposed mice by increasing 5-hydroxytryptamine (5-HT) and dopamine (DA) levels, alleviating hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and increasing BDNF expression. In conclusion, the findings of the current study extensive evidence for the application of loganin in stress-associated disorders, specifically targeting depression.

摘要

民族药理学相关性

山茱萸是一种珍贵的草药,常用于中医临床。马钱苷是从传统中药山茱萸果实中获得的主要环烯醚萜苷。马钱苷已被证明能改善急性应激小鼠的抑郁样行为,可能是一种潜在的抗抑郁候选药物。

研究目的

评估马钱苷对慢性不可预测轻度应激(CUMS)诱导的抑郁样小鼠的影响,并探讨其作用机制。

材料与方法

采用CUMS刺激法诱导ICR小鼠抑郁。通过一系列行为测试,如蔗糖偏好试验(SPT)、强迫游泳试验(FST)、悬尾试验(TST)和旷场试验(OFT),评估马钱苷对抑郁样行为的治疗效果。此外,采用酶联免疫吸附测定法(ELISA)检测促肾上腺皮质激素(ACTH)和皮质酮(CORT)的血清水平。通过高效液相色谱 - 电化学检测法(HPLC - ECD)检测单胺类神经递质水平。采用蛋白质免疫印迹分析检测海马中脑源性神经营养因子(BDNF)的水平。

结果

结果表明,行为测试显示CUMS诱导了小鼠的抑郁样行为。给予马钱苷可增加SPT中的蔗糖偏好,同时减少FST和TST中的不动时间。马钱苷还可改善食物摄入量,并增加OFT中的穿越次数。在机制方面,马钱苷将单胺类神经递质、ACTH和CORT的分泌恢复到正常水平。此外,马钱苷提高了海马中BDNF的表达。总之,马钱苷通过调节单胺类神经递质、ACTH、CORT和BDNF在CUMS模型小鼠中发挥抗抑郁样作用。

结论

马钱苷通过增加5 - 羟色胺(5 - HT)和多巴胺(DA)水平、缓解下丘脑 - 垂体 - 肾上腺(HPA)轴功能障碍以及增加BDNF表达,有效改善了CUMS暴露小鼠的抑郁样症状。总之,本研究结果为马钱苷在应激相关疾病,特别是抑郁症中的应用提供了广泛的证据。

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