Cryptotanshinone ameliorates CUS-induced depressive-like behaviors in mice

Kaixin Wang; Qingling Zhai; Sanwang Wang; Qiongyu Li; Jing Liu; Fantao Meng; Wentao Wang; Jinjie Zhang; Dan Wang; Di Zhao; Cuilan Liu; Juanjuan Dai; Chen Li; Minghu Cui; Jinbo Chen

doi:10.1515/tnsci-2020-0198

Cryptotanshinone ameliorates CUS-induced depressive-like behaviors in mice

Transl Neurosci. 2021 Nov 30;12(1):469-481. doi: 10.1515/tnsci-2020-0198. eCollection 2021 Jan 1.

Authors

Kaixin Wang^{1

2

3

4}, Qingling Zhai^{1

2

3}, Sanwang Wang^{2

3

5}, Qiongyu Li⁶, Jing Liu^{2

3}, Fantao Meng^{2

3}, Wentao Wang^{2

3}, Jinjie Zhang^{2

3}, Dan Wang^{2

3}, Di Zhao^{2

3}, Cuilan Liu^{2

3}, Juanjuan Dai², Chen Li^{2

3}, Minghu Cui⁵, Jinbo Chen¹

Affiliations

¹ Department of Neurology, Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Binzhou, Shandong, 256603, China.
² Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong, China.
³ Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong, China.
⁴ Department of Internal Medicine, Jinan Hospital, Jinan, Shandong, China.
⁵ Department of Psychology, Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Binzhou, Shandong, 256603, China.
⁶ Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China.

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.

Keywords: BDNF; cryptotanshinone; depression; microglial polarization; neurogenesis; neuroinflammation.