Cryptotanshinone ameliorates CUS-induced depressive-like behaviors in mice

Abstract

Objectives Cryptotanshinone (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. Methods We 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. Results Administration 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. Conclusions CPT 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.

Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats

“…Behavioral analyses of mechanical allodynia have revealed recovery after cAMP/PKA/CREB signaling is inhibited with a PKA inhibitor, suggesting that the effects of the PKA inhibitor may occur through regulation of mechanical allodynia [32]. Interestingly, the PKA inhibitors H-89 and PKI (14)(15)(16)(17)(18)(19)(20)(21)(22) can block the regulation of CGRP release and regulate pain sensitization [33].…”

“…The reaction conditions were as follows: 95°C for 15 minutes; 40 cycles of 94°C for 15 seconds, 55°C for 30 seconds and 72°C for 45 seconds; extentioning at 72 °C for 10 minutes. Compared with the control sample, the 2 −ΔΔCT method was performed to obtain the relative fold change of the PACAP normalized by the GAPDH [ 20 ].…”

Adult hippocampal neurogenesis: pharmacological mechanisms of antidepressant active ingredients in traditional Chinese medicine

“…Cryptotanshinone, a natural quinone diterpenoid extracted from Salvia miliorrhiza , employs the BDNF/TrKB and NFκB signaling pathways to promote AHN and inhibit neuroinflammation[], thus exerting its antidepressant mechanism ( Wang et al, 2021 ). Naringin, a bioflavonoid identified from Tangerine Peel , promotes AHN and treats depression by activating the CREB signaling pathway ( Gao et al, 2022 ).…”

Effect of Cryptotanshinone on BDNF/TrkB Pathway in Hippocampus of Chronic Stress-induced Depression Rats

“…Recently, we investigated the potent activity of CTS in mice with different depression models induced by various drugs such as corticosterone, reserpine, and 5-HTP (Chen, Chen, et al, 2021; Chen, Liao, et al, 2021). Moreover, CTS is also effective in chronic unpredictable mild stress (CUMS)-induced depression mice (Wang et al, 2021). However, the positive control group is lacking, and the dose-dependent effects are still needed to be elucidated.…”