Liu Dingding, Wang Jingru, Chang Lulu, Zhu Qiang, Jiang Ning, Azhar Mudassar, Zeng Guirong
College of Pharmacy & Research Center for Pharmacodynamic Material Basis and Mechanism of Action, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
J Ethnopharmacol. 2022 Jul 15;293:115253. doi: 10.1016/j.jep.2022.115253. Epub 2022 Apr 4.
Qingyangshen (Cynanchum otophyllum C.K.Schneid.PI.Wilson.) is the folk medicine of Yunnan which is renowned for its use in the management of neuropsychiatric diseases. The isolated glycosides from Qingyangshen have demonstrated relief in the social defeat stress, however, mechanism of action has not yet been elucidated.
This study is aimed to elucidate the effect of Qingyangshen glycosides (QYS) on chronic social defeat stress (CSDS)-induced depression-like symptoms and the related mechanism.
In mice, CSDS model was developed, and the effect of QYS was evaluated by observing the behavioral performance of these mice exposed to tasks related to depression-like activities. Moreover, microscopic pathological examinutesation was also done. Furthermore, the protein expressions related to social defeat stress were also determined to elucidate the possible underlying mechanism.
Our results indicated that QYS treatment reversed the CSDS-induced depressive-like behaviors as measured by the increased sucrose preference, open field activity, and social interactions among mice. The reversal of the morphological changes in the hippocampus of the CSDS mice was also noted. Additionally, QYS treatment also upregulated the silent mating type information regulation 2 homolog 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), fibronectin III domain containing protein 5 (FNDC5), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), and mitogen-activated protein kinase (MAPK) proteins.
Our study indicated that QYS had a good anti-social defeat stress effect on CSDS-induced depression in mice, mainly through SIRT1/PGC-1α/FNDC5/BDNF-TrkB signaling pathway activation.
青阳参(Cynanchum otophyllum C.K.Schneid.PI.Wilson.)是云南的民间药物,以用于治疗神经精神疾病而闻名。从青阳参中分离出的糖苷已显示出对社会挫败应激有缓解作用,然而,其作用机制尚未阐明。
本研究旨在阐明青阳参糖苷(QYS)对慢性社会挫败应激(CSDS)诱导的抑郁样症状的影响及其相关机制。
在小鼠中建立CSDS模型,通过观察这些小鼠在与抑郁样活动相关任务中的行为表现来评估QYS的作用。此外,还进行了微观病理检查。此外,还测定了与社会挫败应激相关的蛋白质表达,以阐明可能的潜在机制。
我们的结果表明,QYS治疗可逆转CSDS诱导的抑郁样行为,表现为小鼠蔗糖偏好增加、旷场活动增加和社交互动增加。还注意到CSDS小鼠海马形态变化的逆转。此外,QYS治疗还上调了沉默交配型信息调节2同源物1(SIRT1)、过氧化物酶体增殖物激活受体-γ共激活因子-1α(PGC-1α)、含纤连蛋白III结构域蛋白5(FNDC5)、脑源性神经营养因子(BDNF)、原肌球蛋白相关激酶B(TrkB)和丝裂原活化蛋白激酶(MAPK)蛋白。
我们的研究表明,QYS对CSDS诱导的小鼠抑郁具有良好的抗社会挫败应激作用,主要通过激活SIRT1/PGC-1α/FNDC5/BDNF-TrkB信号通路。