Activation of the hippocampal AC‐cAMP‐PKA‐CREB‐BDNF signaling pathway using WTKYR in depression model rats

Peng, Yangzhi; Zhang, Chengchen; Su, Yue; Wang, Zewen; Jiang, Yong

doi:10.1002/elps.201800381

Cited by 17 publications

(13 citation statements)

References 18 publications

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“… 30 , 31 The adenylyl cyclase (AC)‐cyclic adenosine monophosphate (cAMP)‐protein kinase A (PKA) signaling system is the best postreceptor signal transduction system. 32 The expression of cAMP‐mediated AQP channels and the expression of G(salpha) were closely connected. 33 Acute closed soft tissue Curing‐injury Cataplasma can promote and regulate the cAMP‐PKA signaling pathways and affect AQP‐3 high expression.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz. and Paeonia lactiflora Pall. in the treatment of functional constipation and its verification

Meng

Wang

et al. 2022

Anim Models and Exp Med

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Background We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz. (AMK) and Paeonia lactiflora Pall. (PLP). Methods The main active ingredients of AMK and PLP were screened by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. A database of functional constipation targets was established by GeneCard and OMIM. An “ingredient‐target” network map was constructed with Cytoscape software (version 3.7.1), and molecular docking analysis was performed on the components and genes with the highest scores. The rats in the normal group were given saline, and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days. The serum and intestinal tissue levels of adenosine monophosphate (cAMP), protein kinase A (PKA), and adenylyl cyclase (AC) of the rats and aquaporin (AQP)1, AQP3, and AQP8 were measured. Results AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. After treatment with AMK, PLP, or mosapride, the serum and intestinal tissue levels of AC, cAMP, and PKA were significantly downregulated. Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1, AQP3, and AQP8 to varying degrees. Conclusion Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. Studies have confirmed that AMK and PLP can also affect AC, cAMP, and PKA. AC, cAMP, and PKA in model rats were significantly downregulated. AQP expression is closely related to AC, cAMP, and PKA. AMK and PLP can reduce the expression of AQP1, AQP3, and AQP9 in the colon of constipated rats.

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Section: Discussionmentioning

confidence: 99%

Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz. and Paeonia lactiflora Pall. in the treatment of functional constipation and its verification

Meng

Wang

et al. 2022

Anim Models and Exp Med

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“…Growth factors and neurotrophic factors play critical roles in the pathogenesis of depression and antidepression responses ( Duman and Li 2012 ; Gao et al, 2017 ). Chronic stress decreases the brain-derived neurotrophic factor (BDNF) and inactivates its receptors, including tropomyosin receptor kinase B (TrkB) and downstream signaling-like cAMP response element-binding protein (CREB) ( Luo et al, 2017 ; Peng et al, 2018 ). Antidepressant treatment elevates BDNF expression and promotes proliferation and differentiation of NSPCs and the maturation of new neurons for hippocampal neurogenesis ( Masi and Brovedani 2011 ; Ma et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Naringin Mediates Adult Hippocampal Neurogenesis for Antidepression via Activating CREB Signaling

Gao

et al. 2022

Front. Cell Dev. Biol.

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The brain-derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element-binding protein (BDNF/TrkB/CREB) signaling pathway is a critical therapeutic target for inducing adult hippocampal neurogenesis and antidepressant therapy. In this study, we tested the hypothesis that naringin, a natural medicinal compound, could promote adult hippocampal neurogenesis and improve depression-like behaviors via regulating the BDNF/TrkB/CREB signaling pathway. We first investigated the effects of naringin on promoting adult hippocampal neurogenesis in both normal and chronic corticosterone (CORT)-induced depressive mice. Under physiological condition, naringin treatment enhanced the proliferation of neural stem/progenitor cells (NSPCs) and accelerated neuronal differentiation. In CORT-induced depression mouse model, naringin treatment promoted neuronal differentiation and maturation of NSPCs for hippocampal neurogenesis. Forced swim test, tail suspension test, and open field test confirmed the antidepressant and anxiolytic effects of naringin. Co-treatment of temozolomide (TMZ), a neurogenic inhibitor, abolished these antidepressant and anxiolytic effects. Meanwhile, naringin treatment increased phosphorylation of cAMP response element binding protein (CREB) but had no effect on the expression of brain-derived neurotrophic factor and phosphorylation of TrkB in the hippocampus of CORT-induced depressive mice. Co-treatment of CREB inhibitor 666-15, rather than TrkB inhibitor Cyc-B, abolished the neurogenesis-promoting and antidepressant effects of naringin. Taken together, naringin has antidepressant and anxiolytic effects, and the underlying mechanisms could be attributed to enhance hippocampal neurogenesis via activating CREB signaling.

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“…Based on literature search, the top 10 significant signaling pathways could involve in the occurrence of depression in varying degrees. For example, pathways in cancer and proteoglycans in cancer indirectly change the probability of depression by influencing HPA axis function ( Young and Singh, 2018 ); Neuroactive ligand-receptor interaction, cocaine addiction and dopaminergic synapse could affect the occurrence of depression through regulating dopamine levels, emotion, learning and memory functions ( Haile et al, 2007 ; Yang et al, 2017 ; Sun et al, 2018 ); cAMP signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway, glutamatergic synapse and gap junction could intervene the occurrence of depression by mediating neural plasticity ( Hennebelle et al, 2014 ; Crider and Pillai, 2017 ; Peng et al, 2018 ; Ren et al, 2018 ; Wu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression

et al. 2021

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Objectives: To evaluate the pharmacodynamical effects and pharmacological mechanism of Ginsenoside H dripping pills (GH) in chronic unpredictable mild stress (CUMS) model rats.Methods: First, the CUMS-induced rat model was established to assess the anti-depressant effects of GH (28, 56, and 112 mg/kg) by the changes of the behavioral indexes (sucrose preference, crossing score, rearing score) and biochemical indexes (serotonin, dopamine, norepinephrine) in Hippocampus. Then, the components of GH were identified by ultra-performance liquid chromatography-iron trap-time of flight-mass spectrometry (UPLC/IT-TOF MS). After network pharmacology analysis, the active ingredients of GH were further screened out based on OB and DL, and the PPI network of putative targets of active ingredients of GH and depression candidate targets was established based on STRING database. The PPI network was analyzed topologically to obtain key targets, so as to predict the potential pharmacological mechanism of GH acting on depression. Finally, some major target proteins involved in the predictive signaling pathway were validated experimentally.Results: The establishment of CUMS depression model was successful and GH has antidepressant effects, and the middle dose of GH (56 mg/kg) showed the best inhibitory effects on rats with depressant-like behavior induced by CUMS. Twenty-eight chemical components of GH were identified by UPLC/IT-TOF MS. Subsequently, 20(S)-ginsenoside Rh2 was selected as active ingredient and the PPI network of the 43 putative targets of 20(S)-ginsenoside Rh2 containing in GH and the 230 depression candidate targets, was established based on STRING database, and 47 major targets were extracted. Further network pharmacological analysis indicated that the cAMP signaling pathway may be potential pharmacological mechanism regulated by GH acting on depression. Among the cAMP signaling pathway, the major target proteins, namely, cAMP, PKA, CREB, p-CREB, BDNF, were used to verify in the CUMS model rats. The results showed that GH could activate the cAMP-PKA-CREB-BDNF signaling pathway to exert antidepressant effects.Conclusions: An integrative pharmacology-based pattern was used to uncover that GH could increase the contents of DA, NE and 5-HT, activate cAMP-PKA-CREB-BDNF signaling pathway exert antidepressant effects.

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Activation of the hippocampal AC‐cAMP‐PKA‐CREB‐BDNF signaling pathway using WTKYR in depression model rats

Cited by 17 publications

References 18 publications

Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz. and Paeonia lactiflora Pall. in the treatment of functional constipation and its verification

Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz. and Paeonia lactiflora Pall. in the treatment of functional constipation and its verification

Naringin Mediates Adult Hippocampal Neurogenesis for Antidepression via Activating CREB Signaling

An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression

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