1. Academic Validation
  2. Tanshinone IIA improves contextual fear- and anxiety-like behaviors in mice via the CREB/BDNF/TrkB signaling pathway

Tanshinone IIA improves contextual fear- and anxiety-like behaviors in mice via the CREB/BDNF/TrkB signaling pathway

  • Phytother Res. 2022 Oct;36(10):3932-3948. doi: 10.1002/ptr.7540.
Yong-Li Jiang 1 Xin-Shang Wang 2 Xu-Bo Li 2 An Liu 1 Qing-Yu Fan 2 Le Yang 1 Ban Feng 2 Kun Zhang 2 Liang Lu 2 Jing-Yu Qi 2 Fan Yang 1 Da-Ke Song 2 Yu-Mei Wu 2 Ming-Gao Zhao 1 Shui-Bing Liu 2
Affiliations

Affiliations

  • 1 Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
  • 2 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Abstract

Posttraumatic stress disorder (PTSD) is one of the most common psychiatric diseases, which is characterized by the typical symptoms such as re-experience, avoidance, and hyperarousal. However, there are few drugs for PTSD treatment. In this study, conditioned fear and single-prolonged stress were employed to establish PTSD mouse model, and we investigated the effects of Tanshinone IIA (TanIIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza, as well as the underlying mechanisms in mice. The results showed that the double stress exposure induced obvious PTSD-like symptoms, and TanIIA administration significantly decreased freezing time in contextual fear test and relieved anxiety-like behavior in open field and elevated plus maze tests. Moreover, TanIIA increased the spine density and upregulated synaptic plasticity-related proteins as well as activated CREB/BDNF/TrkB signaling pathway in the hippocampus. Blockage of CREB remarkably abolished the effects of TanIIA in PTSD model mice and reversed the upregulations of p-CREB, BDNF, TrkB, and synaptic plasticity-related protein induced by TanIIA. The molecular docking simulation indicated that TanIIA could interact with the CREB-binding protein. These findings indicate that TanIIA ameliorates PTSD-like behaviors in mice by activating the CREB/BDNF/TrkB pathway, which provides a basis for PTSD treatment.

Keywords

CREB/BDNF/TrkB pathway; Tanshinone IIA; conditioned fear; posttraumatic stress disorder; single-prolonged stress; synaptic plasticity.

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