Abstract
ObjectivesCryptotanshinone (CPT), a natural quinoid diterpene, isolated from Salvia miltiorrhiza, has shown various pharmacological properties. However, its effect on chronic unpredictable stress (CUS)-induced depression phenotypes and the underlying mechanism remain unclear. Therefore, the aim of this study was to investigate whether CPT could exert an antidepressant effect.MethodsWe investigated the effects of CPT in a CUS-induced depression model and explored whether these effects were related to the anti-inflammatory and neurogenesis promoting properties by investigating the expression levels of various signaling molecules at the mRNA and protein levels.ResultsAdministration of CPT improved depression-like behaviors in CUS-induced mice. CPT administration increased the levels of doublecortin-positive cells and reversed the decrease in the expression levels of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling transduction, as well as the downstream functional proteins, phosphorylated extracellular regulated protein kinases (p-ERK), and cyclic adenosine monophosphate (cAMP)-response element-binding protein levels (p-CREB) in hippocampus. CPT treatment also inhibited the activation of microglia and suppressed M1 microglial polarization, while promoting M2 microglial polarization by monitoring the expression levels of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS), and further inhibited the expression of proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), and increased the expression of the anti-inflammatory cytokine IL-10 by regulating nuclear factor-κB (NF-κB) activation.ConclusionsCPT relieves the depressive-like state in CUS-induced mice by enhancing neurogenesis and inhibiting inflammation through the BDNF/TrkB and NF-κB pathways and could therefore serve as a promising candidate for the treatment of depression.
Highlights
Depression, one of the most prevalent psychiatric disorders, is a significant public health problem globally andThis work is licensed under the Creative Commons Attribution 4.0470 Kaixin Wang et al.places a substantial burden on socioeconomic development [1]
Our results indicated that there were significant effects on CPT treatment (F(2,21) = 6.520, p = 0.006), sniffing objects (F(1,21) = 67.530, p < 0.001), and treatment × sniffing objects interaction (F(2,21) = 7.232, p = 0.004), and further analysis showed that chronic unpredictable stress (CUS) obviously decreased the sniffing duration (p < 0.001), which was restored by CPT (p < 0.001), whereas no differences in water sniffing time were observed between the three groups (Figure 2c, p > 0.05, p > 0.05)
We found that CPT alleviated the CUS induced depression-related phenotypes by promoting neurogenesis and Brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling and inhibiting microglial activation and the release of proinflammatory factors in CUS mice
Summary
Depression, one of the most prevalent psychiatric disorders, is a significant public health problem globally andThis work is licensed under the Creative Commons Attribution 4.0470 Kaixin Wang et al.places a substantial burden on socioeconomic development [1]. Studies have shown that neurogenesis and neuroinflammation play important roles in the pathogenesis of depression [5,6,7]. Neurogenesis is mainly promoted by neural progenitor cells located in the granular zone of the dentate gyrus (DG) to produce new neurons. After these new neurons are generated, they proliferate, migrate, and differentiate and are subsequently integrated into the existing neuronal circuits to form synaptic connections [11]. Brain-derived neurotrophic factor (BDNF) is widely distributed in the brain and plays an important role in the survival, development, and growth of central neurons [12] and is involved in the regulation of neurogenesis [13]. Decreased BDNF levels and abnormal neurogenesis are associated with depressive symptoms and behaviors [14,15,16]
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