Echinacoside exhibits antidepressant-like effects through AMPAR–Akt/ERK–mTOR pathway stimulation and BDNF expression in mice

Chinese Medicine

I-Hua Wei¹  Tse-Yen Wang²  Han-Wen Chuang³  Chih-Chia Huang⁴ 

[1] Department of Anatomy, China Medical University, Taichung, Taiwan;Department of Post-baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan;Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan;Department of Psychiatry, China Medical University, Taichung, Taiwan;Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan;Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan;

关键词: AMPAR;    Akt;    ERK;    mTOR;    Echinacoside;    Antidepressant;   

DOI  :  10.1186/s13020-021-00549-5

来源: Springer

【 摘 要 】

BackgroundSeveral natural products have been demonstrated to be effective in the treatment of depressive disorders. Echinacoside, a naturally occurring phenol extracted from Cistanche tubulosa, Echinacea angustifolia, and Cistanche spp, has a wide range of physiological effects, such as antioxidation, neuroprotection, anti-inflammatory, and immunoregulation, which are closely related to depression. In addition, echinacoside can activate protein kinase B (Akt), extracellular signal–regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) in the brain. A key downstream event of the Akt, ERK, and BDNF signaling pathways, namely mechanistic target of rapamycin (mTOR) signaling, plays a crucial role in generating an rapid antidepressant effect. Thus, echinacoside is a promising therapeutic agent for depression. However, research regarding the role of echinacoside in antidepressant effect and brain mTOR activation remains lacking.Materials and methodsThe forced swimming test and Western blot analysis in C57BL/6 mice was used to investigate the antidepressant-like activities of echinacoside and the underlying mechanism involved inα-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)–Akt/ERK–mTOR pathway.ResultsWe confirmed the suggestions by previous reports that echinacoside activates Akt/ERK signaling and further demonstrated that echinacoside could provide antidepressant-like effects in mice via the activation of AMPAR–Akt/ERK–mTOR pathway in the hippocampus.ConclusionsTo the best of our knowledge, our study is the first to reveal that echinacoside is a potential treatment for depressive disorders. Moreover, the present study suggests a mechanism for the neuroprotective effect of echinacoside.

【 授权许可】

CC BY