scholarly journals Network pharmacology and the experimental findings of Bushenhuoxue formula for improving hippocampal neuron injury in vascular demented rats

2021 ◽  
Vol 20 (4) ◽  
pp. 847-859
Author(s):  
Shan Luo ◽  
Jiaxing Jing ◽  
Ying Zhang ◽  
Wentao Yu ◽  
Weijuan Gao
2020 ◽  
Author(s):  
Fangxian Liu ◽  
Qijin Pan ◽  
Liangliang Wang ◽  
Shijiang Yi ◽  
Peng Liu ◽  
...  

Abstract Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jie Ma ◽  
Qunfang Yang ◽  
Yuling Wei ◽  
Yang Yang ◽  
Chaonan Ji ◽  
...  

1998 ◽  
Vol 43 (5) ◽  
pp. 664-669 ◽  
Author(s):  
Kelvin A. Yamada ◽  
Douglas F. Covey ◽  
Chung Y. Hsu ◽  
Rong Hu ◽  
Yuefei Hu ◽  
...  

Cell Cycle ◽  
2019 ◽  
Vol 18 (22) ◽  
pp. 3206-3222 ◽  
Author(s):  
Xiangyong Feng ◽  
Wei Xiong ◽  
Mingqiong Yuan ◽  
Jian Zhan ◽  
Xiankun Zhu ◽  
...  

2021 ◽  
Author(s):  
Zong Chen ◽  
Yong Ding ◽  
Ying Zeng ◽  
Xue-Ping Zhang ◽  
Jian-Yan Chen

Abstract BackgroundPropofol and dexmedetomidine (DEX) are widely used in general anesthesia, and exert toxic and protective effects on hippocampal neurons, respectively. The study sought to investigate the molecular mechanisms of DEX-mediated neuroprotection against propofol-induced hippocampal neuron injury in mouse brains.MethodsHippocampal neurons of mice were treated with propofol, DEX, and propofol+DEX in vitro and in vivo. Neuronal apoptosis was evaluated by a means of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) or Hochest 33258 staining; Arc positive expression in hippocampus tissues was detected using a microscope in immunohistochemistry assays; miRNA-377-5p expression levels were quantified by RT-PCR; the protein levels of Arc, DNMT3A, and DNMT3B were determined using western blot; CCK-8 kit was used to evaluated neuron viability; methylation analysis in miR-377-5p promoter was performed through the methylated DNA immunoprecipitation (MeDIP) assay; luciferase reporter assay was performed to confirm whether Arc was under targeted regulation of miR-377-5p.Results In the current study, both in vitro and in vivo, propofol treatment induced hippocampal neuron apoptosis and suppressed cell viability. DNMT3A and DNMT3B expression levels were decreased following propofol treatment, resulting in lowered methylation in the miR-377-5p promoter region and then enhanced expression of miR-377-5p, leading to a decrease in the expression level of downstream Arc. Conversely, the expression levels of DNMT3A and DNMT3B were increased following DEX treatment, thus methylation in miR-377-5p promoter region was improved, and miR-377-5p expression levels were decreased, leading to an increase in the expression level of downstream Arc. Finally, DEX pretreatment protected hippocampal neurons against propofol-induced neurotoxicity by recover the expression levels of DNMT3A, miR-377-5p, and Arc to the normal levels.ConclusionsDEX reduced propofol-induced hippocampal neuron injury via the miR-377-5p/Arc signaling pathway.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guangchan Jing ◽  
Huanyuan Wang ◽  
Fengwei Nan ◽  
Yuqin Liu ◽  
Mengren Zhang

P2X7/NLRP1/caspase-1 mediated neuronal injury plays an important role in diabetic cognitive impairment and eventually inflammatory cascade reaction. Chinese herbal compound Naofucong has been mainly used to treat cognitive disorders in Traditional Chinese Medicine The present study aimed to investigate whether its neuroprotective effects might be related to the inhibition of P2X7R/NLRP1/caspase-1 mediated neuronal injury or not. In this study, high glucose-induced HT22 hippocampal neurons were used to determine Naofucong-containing serum neuronal protective effects. Lentiviruses knock out of TXNIP and P2X7R was used to determine that protective effects of Naofucong was related to inflammatory response and P2X7/NLRP1/caspase-1 mediated neuronal injury. NAC was also used to inhibit oxidative stress, so as to determine that oxidative stress is an important starting factor for neuronal injury of HT22 cells cultured with high glucose. Naofucong decreased apoptosis, IL-1β and IL-18 levels in high glucose-induced HT22 hippocampal neuron cells. Naofucong suppressed NLRP1/caspase-1 mediated neuronal injury, and P2X7 was involved in process. HT22 cells cultured in high glucose had an internal environment with elevated oxidative stress, which could promote neuronal injury. The current study demonstrated that Naofucong could significantly improve high glucose-induced HT22 hippocampal neuron injury, which might be related to suppress P2X7R/NLRP1/caspase-1 pathway, which provides novel evidence to support the future clinical use of Naofucong.


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