1. Academic Validation
  2. Rosmarinic acid alleviate CORT-induced depressive-like behavior by promoting neurogenesis and regulating BDNF/TrkB/PI3K signaling axis

Rosmarinic acid alleviate CORT-induced depressive-like behavior by promoting neurogenesis and regulating BDNF/TrkB/PI3K signaling axis

  • Biomed Pharmacother. 2023 Dec 8:170:115994. doi: 10.1016/j.biopha.2023.115994.
Jiuseng Zeng 1 Zhiqiang Xie 2 Li Chen 3 Xi Peng 1 Fei Luan 4 Jingwen Hu 2 Hongxiao Xie 2 Rong Liu 2 Nan Zeng 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
  • 2 Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
  • 3 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacy, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China.
  • 4 School of Pharmacy, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China.
  • 5 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: 19932015@cdutcm.edu.cn.
Abstract

Rosmarinic acid (RA), a natural phenolic acid compound with a variety of bioactive properties. However, the antidepressant activity and mechanism of RA remain unclear. The aim of this study is to investigate the effects and potential mechanisms of RA on chronic CORT injection induced depression-like behavior in mice. Male C57BL/6 J mice were intraperitoneally injected with CORT (10 mg/kg) and were orally given RA daily (10 or 20 mg/kg) for 21 consecutive days. In vitro, the HT22 cells were exposed to CORT (200 μM) with RA (12.5, 25 or 50 μM) and LY294002 (a PI3K Inhibitor) or ANA-12 (a TrkB Inhibitor) treatment. The depression-like behavior and various neurobiological changes in the mice and cell injury and levels of target proteins in vitro were subsequently assessed. Here, RA treatment decreased the expression of p-GR/GR, HSP90, FKBP51, SGK-1 in mice hippocampi. Besides, RA increased the average optical density of Nissl bodies and number of dendritic spines in CA3 region, and enhanced Brdu and DCX expression and synaptic transduction in DG region, as well as up-regulated both the BDNF/TrkB/CREB and PI3K/Akt/mTOR signaling. Moreover, RA reduced structural damage and Apoptosis in HT22 cells, increased the differentiation and maturation of them. More importantly, LY294002, but not ANA-12, reversed the effect of RA on GR nuclear translocation. Taken together, RA exerted antidepressant activities by modulating the hippocampal glucocorticoid signaling and hippocampal neurogenesis, which related to the BDNF/TrkB/PI3K signaling axis regulating GR nuclear translocation, provide evidence for the application of RA as a candidate for depression.

Keywords

Antidepressant; BDNF/TrkB/PI3K signaling axis; Glucocorticoid receptor; HPA axis; Neurogenesis; Rosmarinic acid.

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