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

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.

Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress

“…In the context of our behavioral experiments that confirm that AR significantly alleviates PTSD-like phenotype in SPS rats, these molecular studies suggest that AR’s neuroprotective effects in SPS rats may be ascribed to its positive effects on synaptic plasticity and inhibition of neuronal apoptosis. A large number of preclinical studies have investigated the therapeutic effects of drugs or other therapeutic strategies on PTSD symptoms by studying changes in synaptic plasticity and neuronal apoptosis ( Li et al, 2013 ; Ji et al, 2019 ; Feng et al, 2020 ; Jiang et al, 2022 ; Li et al, 2022 ): e.g., Sevoflurane has been shown to attenuate apoptosis and improve synaptic plasticity in the hippocampus of rat models of PTSD ( Gu et al, 2023 ), and down-regulating MiR-153 has been observed to alleviate PTSD-like behaviors by affecting synaptic plasticity and apoptosis ( Chen et al, 2022 ). Hence, the present findings that AR enhances synaptic plasticity and inhibits neuronal apoptosis suggest that it has potential as an effective therapeutic agent in the treatment of PTSD.…”

Glucosyl hesperidin exhibits more potent anxiolytic activity than hesperidin accompanied by the attenuation of noradrenaline induction in a zebrafish model

“…Thus, this pathway has been considered a target for a drug investigation. Several compounds or extracts from natural products, such as darmmarane sapogenins originating from ginseng ( Jiang et al, 2020 ), tannins from Terminalia chebula fruits ( Chandrasekhar et al, 2018 ), and diterpene quinone Tanshinone IIA isolated from the roots of Salvia miltiorrhiza Bunge ( Jiang et al, 2022 ), attenuate anxiety by activating the CREB/BDNF pathways. Flavonoids are also reported to attenuate mental disorders involved in CREB/BDNF pathway, such as rutin ( Moghbelinejad et al, 2014 ), baicalin ( Jia et al, 2021 ), and naringin ( Gao et al, 2022 ).…”

Bile acid signalling and its role in anxiety disorders

“…Similarly, HPA axis dysfunction caused by endocrine disorders is an inducing or aggravating factor for anxiety ( 93 – 95 ). Recent studies have shown that regulating FGFR can affect BDNF expression ( 96 ) and that the BDNF-TrkB signaling pathway plays an important role in anxiety ( 96 , 97 ). The overexpression of serum CDCA over-activates intestinal FXR receptors, resulting in an imbalance in the FGFs/FGFRs system that impacts the BDNF-TrkB signal pathway, which finally culminates in anxiety-like behavior.…”