scholarly journals Helicid Reverses the Effect of Overexpressing NCALD, Which Blocks the sGC/cGMP/PKG Signaling Pathway in the CUMS-Induced Rat Model

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiao-Tong Zhang ◽  
Yuan Zhang ◽  
Yuan-Xiang Zhang ◽  
Zhen-Yi Jiang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Rat Model ◽  
Caspase 3 ◽  
Underlying Mechanism ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Adeno Associated Virus ◽  
Protein Levels ◽  
Antidepressant Effects

Background. Increasing evidence has shown that apoptosis in the hippocampus is closely related to depressive-like behavior. We previously reported that helicid had good antidepressant activities, which manifested as the alleviation of depression-like behaviors and the reversal of the high expression of neurocalcin delta (NCALD) in chronic unpredictable mild stress (CUMS) rats. The aim of this study was, therefore, to characterize the antidepressant-like effects and underlying mechanism of helicid on CUMS rats by silencing NCALD and using rescue experiments. Methods. We developed the CUMS rat model using CUMS stimulation from week 0 to week 6. The rats were treated with helicid, or NCALD silenced, then we overexpressed NCALD using adeno-associated virus. We also measured the protein levels of sGCα1, sGCβ1, PKG1/2, and cleaved caspase-3 in hippocampal tissues using western blotting and measured cGMP using an ELISA. Results. Treating CUMS rats by silencing NCALD or by the administration of helicid improved the depressive-like behavior. The levels of proteins, including sGC, PKG, cleaved caspase-3, and cGMP, in hippocampus all decreased. NCALD overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. Limitation. We only detected the antidepressant effects of helicid in the hippocampus; therefore, other parts of brain should also be studied. Conclusions. Inhibition of NCALD, as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing NCALD reversed the amelioration effects of silenced NCALD and helicid administration.

scholarly journals Effect of Electroacupuncture on Reuptake of Serotonin via miRNA-16 Expression in a Rat Model of Depression

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Jun Zhao ◽  
Huiling Tian ◽  
Hongtao Song ◽  
Xu Wang ◽  
Tong Luo ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Rat Model ◽  
Exploratory Behavior ◽  
Continuous Wave ◽  
Behavioral Changes ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Antidepressant Effects

The current study aimed to investigate the effects and mechanisms of electroacupuncture (EA) treatment applied to Bai hui (GV20) and Yin tang (GV29) acupoints (1 mA, 2 Hz, continuous wave, 20 minutes) for 28 days in a rat model of chronic unpredictable mild stress (CUMS) on reuptake of serotonin (5-hydroxytryptamine (5-HT)) and miRNA-16 levels in the hippocampus and serum. Rats were housed in individual cages, and CUMS was used to establish a rat model of depression. After EA treatment for 4 weeks, behavioral changes and indices including 5-HT transporter (SERT), 5-HT, and miRNA-16 levels in the hippocampus and serum were examined. The EA treatment significantly improved base levels of sucrose preference and exploratory behavior and significantly decreased SERT protein and mRNA expression in the hippocampus of depressed rats. Significantly increased 5-HT levels were observed, and miRNA-16 levels were significantly decreased in the hippocampus and serum of depressed rats. In conclusion, the antidepressant effects of EA treatment may be affected via inhibition of 5-HT reuptake, upregulation of 5-HT levels, and inhibition of miRNA-16 expression in the hippocampus and serum.

Network Pharmacology Analysis of the Effects of Achyranthis Bidentatae Radix Plus Semen Vaccariae on Migraine-Induced Erectile Dysfunction

2021 ◽  
Vol 24 ◽  
Author(s):  
Jisheng Wang ◽  
Junlong Feng ◽  
Sheng Deng ◽  
Binghao Bao ◽  
Fanchao Meng ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Rat Model ◽  
Network Pharmacology ◽  
Histological Structure ◽  
Protein Levels ◽  
Hematoxylin And Eosin ◽  
Regulatory Effects ◽  
Group B

Background and aim: Achyranthis Bidentatae Radix plus Semen Vaccariae are traditional Chinese medicines, which have been widely applied in the treatment of migraine and erectile dysfunction (ED) for many years. The aim of this study is to verify the effect of Achyranthis Bidentatae Radix plus Semen Vaccariae in improving migraine-induced ED and explore its potential mechanism. Methods: Key targets and signaling pathways of Achyranthis Bidentatae Radix plus Semen Vaccariae in migraine-induced erectile dysfunction treatment were predicted by network pharmacology. A rat model of migraine was established by nitroglycerin injection. Apomorphine was injected into rats to screen the migraine-induced erectile dysfunction model, Achyranthis Bidentatae Radix-Semen Vaccariae granule suspension administered, and erectile function evaluated. Hematoxylin and eosin staining was used to compare the histological structure of the penile tissue, while RT-qPCR and Western blotting were used to determine mRNA and protein levels, respectively. Results: Screening allowed us to identify common targets for migraine and ED; the signaling pathway exhibiting the greatest change the Myosin light chain kinase- Calcium (MLCK-CaM) signal pathway. From Western blotting and RT-qPCR, we found that the levels of MLCK mRNA and protein in rats from Group B rats were significantly higher (P<0.05) than those in Groups A and C. Furthermore, the mRNA and protein levels of CaM were significantly higher in Group B (P<0.05) than in Groups A and C. Conclusion: Data indicate that the regulatory effects of Achyranthis Bidentatae Radix plus Semen Vaccariae on migraine-induced ED in a rat model are mediated by the MLCK-CaM signaling pathway.

scholarly journals Sulforaphane Attenuates Endometriosis in Rat Models Through Inhibiting PI3K/Akt Signaling Pathway

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581985553 ◽  
Author(s):  
Aixiu Zhou ◽  
Yiting Hong ◽  
Yuchun Lv
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Akt Signaling Pathway ◽  
Tnf Α ◽  
Ifn Γ

Sulforaphane exerts anti-inflammatory activity in inflammatory diseases. The endometriosis (EM) is accompanied by chronic inflammation. The present study aims to explore the therapeutic effects of sulforaphane on EM and its underlying mechanism. An EM rat model was established by transplantation of autologous fragments. The rats were intragastrically administered sulforaphane (5 mg/kg, 15 mg/kg, and 30 mg/kg) for 3 weeks. The volumes of endometriotic foci and adhesion score were calculated at the end of the experiment. Levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA). Expressions of VEGF, B-cell lymphoma/leukemia 2 (Bcl-2), Bax, cleaved caspase-3, PI3K, and Akt in endometrial tissue were determined by Western blotting. Relative expressions of PI3K and Akt were determined by quantitative polymerase chain reaction. Posttreatment of sulforaphane dose-dependently decreased the volumes of endometriotic foci and adhesion score in EM model. Additionally, posttreatment of sulforaphane inhibited levels of IL-6, IL-10, TNF-α, IFN-γ, and VEGF in peritoneal fluid and plasma. Posttreatment of sulforaphane regulated the expressions of VEGF, bcl-2, Bax, and cleaved Caspase-3 in EM model. The underlying mechanism revealed that sulforaphane attenuated EM in the rat model by inhibition of PI3K/Akt signaling pathway.

scholarly journals (Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose

2015 ◽  
Vol 309 (3) ◽  
pp. E302-E310 ◽  
Author(s):  
Caixia Li ◽  
Helmy M. Siragy
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Autophagic Flux ◽  
Bafilomycin A1 ◽  
Mtor Signaling Pathway ◽  
Autophagosome Formation ◽  
Podocyte Injury ◽  
Protein Levels

High glucose reduces autophagy and enhances apoptosis of podocytes. Previously, we reported that high glucose induced podocyte injury through upregulation of the (pro)renin receptor (PRR). We hypothesized that increasing PRR reduces autophagy and increases apoptosis of mouse podocytes exposed to high glucose via activation of the PI3K/Akt/mTOR signaling pathway. Mouse podocytes were cultured in normal (5 mmol/l) or high (25 mmol/l) d-glucose for 48 h. High glucose significantly increased mRNA and protein levels of PRR, phosphorylation of PI3K/Akt/mTOR, and p62. In contrast, high glucose decreased activation of UNC-51-like kinase-1 (ULK1) by phosphorylating Ser757 and protein levels of microtubule-associated protein-1 light chain 3B (LC3B)-II and Lamp-2. Bafilomycin A1 increased LC3BII and p62 accumulation in high-glucose-treated cells. High glucose reduced the autophagic flux. Confocal microscopy studies showed significant reduction in the protein level of LC3B in response to high glucose. Cyto-ID autophagy staining showed a significant decrease in autophagosome formation with high glucose. In the absence of PRR, activation of Akt with sc-79 or mTOR with MHY-1485 increased p62 accumulation. Caspase-3/7 activity and apoptosis monitored by TUNEL assay were significantly increased in podocytes treated with high glucose. PRR siRNA significantly reversed the effects of high glucose. Based on these data, we conclude that high glucose decreases autophagy and increases apoptosis in mouse podocytes through the PRR/PI3K/Akt/mTOR signaling pathway.

scholarly journals Antidepressant Effects of Rhodomyrtone in Mice with Chronic Unpredictable Mild Stress-Induced Depression

2018 ◽  
Vol 22 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Huihui Chai ◽  
Bin Liu ◽  
Haoqiang Zhan ◽  
Xueqian Li ◽  
Zhipeng He ◽  
...  
Keyword(s):  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Antidepressant Effects
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