Integrating systematic pharmacology-based strategy and experimental validation to explore the synergistic pharmacological mechanisms of Guanxin V in treating ventricular remodeling

et al. 2021

Front. Mol. Biosci.

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Glioblastoma multiform is a lethal primary brain tumor derived from astrocytic, with a poor prognosis in adults. Reticulocalbin-1 (RCN1) is a calcium-binding protein, dysregulation of which contributes to tumorigenesis and progression in various cancers. The present study aimed to identify the impact of RCN1 on the outcomes of patients with Glioblastoma multiforme (GBM). The study applied two public databases to require RNA sequencing data of Glioblastoma multiform samples with clinical data for the construction of a training set and a validation set, respectively. We used bioinformatic analyses to determine that RCN1 could be an independent factor for the overall survival of Glioblastoma multiform patients. In the training set, the study constructed a predictive prognostic model based on the combination of RCN1 with various clinical parameters for overall survival at 0.5-, 1.0-, and 1.5-years, as well as developed a nomogram, which was further validated by validation set. Pathways analyses indicated that RCN1 was involved in KEAS and MYC pathways and apoptosis. In vitro experiments indicated that RCN1 promoted cell invasion of Glioblastoma multiform cells. These results illustrated the prognostic role of RCN1 for overall survival in Glioblastoma multiform patients, indicated the promotion of RCN1 in cell invasion, and suggested the probability of RCN1 as a potential targeted molecule for treatment in Glioblastoma multiform.

Section: Methodsmentioning

confidence: 99%

Integrative Analyses and Verification of the Expression and Prognostic Significance for RCN1 in Glioblastoma Multiforme

Chen

et al. 2021

Front. Mol. Biosci.

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“…Lu-Hong Formula can inhibit the expression of TGF-β1, and then inhibit the expression of collagen type I and III, and fibronectin genes and proteins, leading to the inhibition of the proliferation and deposition of collagen in the left ventricle in pressure-overloaded rats ( 69 ). Guanxin V could inhibit the TGF-β1 pathway to exert an anti-VR effect ( 80 ). Bu-Yang-Huan-Wu Decoction, prepared using Radix Astragali (Huangqi), Angelica sinensis (Oliv.)…”

Section: Molecular Pathways Involved In Cardiac Remodelingmentioning

confidence: 99%

“…Li (Dihuang), Salvia miltiorrhiza Bunge (Danshen), and Paeonia lactiflora Pall . (Chishao) ( 80 , 125 ) and has a significant effect on VR ( 126 ). Mechanistically, in an animal model, Guanxin V can inactivate RAAS in VR after acute myocardial infarction through the non-angiotensin converting enzyme pathway, which significantly reduces the level of Ang II, reduces the infarct size after acute myocardial infarction, protect cardiac function, reduce myocardial fibrosis, and thus, reduce VR ( 127 ).…”

Section: Molecular Pathways Involved In Cardiac Remodelingmentioning

confidence: 99%

Cellular and Molecular Mechanism of Traditional Chinese Medicine on Ventricular Remodeling

Zhu

Front. Cardiovasc. Med.

2021

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Ventricular remodeling is related to the renin-angiotensin-aldosterone system, immune system, and various cytokines involved in inflammation, apoptosis, and cell signal regulation. Accumulated studies have shown that traditional Chinese medicine can significantly inhibit the process of ventricular remodeling, which may be related to the mechanism mentioned above. Here, we conducted a system overview to critically review the cellular and molecular mechanism of traditional Chinese medicine on ventricular remodeling. We mainly searched PubMed for basic research about the anti-ventricular remodeling of traditional Chinese medicine in 5 recent years, and then objectively summarized these researches. We included more than 25 kinds of Chinese herbal medicines including Qi-Li-Qian-Xin, Qi-Shen-Yi-Qi Pill, Xin-Ji-Er-Kang Formula, and Yi-Qi-Wen-Yang Decoction, and found that they can inhibit ventricular remodeling effectively through multi-components and multi-action targets, which are promoting the clinical application of traditional Chinese medicine.

“…Network pharmacology is an interdisciplinary subject, its formation and development mainly benefit from artificial intelligence and big data analysis ( 12 ). The primary advantage of the network pharmacology is to emphasize the integrity, systemic, and biological network of the research object ( 13 ), which promotes the transformation of traditional Chinese medicine research method from the “one target, one drug” to “multiple target and multi-components,” thereby the molecular association between the multiple components and multiple targets could be analyzed. This feature more closely coincides with the concept of traditional Chinese medicine ( 14 ), which emphasizes the systemic and integrity in the progress of diagnosis and therapy ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

Potential Mechanism of Dingji Fumai Decoction Against Atrial Fibrillation Based on Network Pharmacology, Molecular Docking, and Experimental Verification Integration Strategy

Front. Cardiovasc. Med.

Wen

et al. 2021

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Background: Dingji Fumai Decoction (DFD), a traditional herbal mixture, has been widely used to treat arrhythmia in clinical practice in China. However, the exploration of the active components and underlying mechanism of DFD in treating atrial fibrillation (AF) is still scarce.Methods: Compounds of DFD were collected from TCMSP, ETCM, and literature. The targets of active compounds were explored using SwissTargetPrediction. Meanwhile, targets of AF were collected from DrugBank, TTD, MalaCards, TCMSP, DisGeNET, and OMIM. Then, the H-C-T-D and PPI networks were constructed using STRING and analyzed using CytoNCA. Meanwhile, VarElect was utilized to detect the correlation between targets and diseases. Next, Metascape was employed for systematic analysis of the mechanism of potential targets and protein complexes in treating AF. AutoDock Vina, Pymol, and Discovery Studio were applied for molecular docking. Finally, the main findings were validated through molecular biology experiments.Results: A total of 168 active compounds and 1,093 targets of DFD were collected, and there were 89 shared targets between DFD and AF. H-C-T-D network showed the relationships among DFD, active compounds, targets, and AF. Three functional protein complexes of DFD were extracted from the PPI network. Further systematic analysis revealed that the regulation of cardiac oxidative stress, cardiac inflammation, and cardiac ion channels were the potential mechanism of DFD in treating AF. Addtionally, molecular docking verified the interactions between active compounds and targets. Finally, we found that DFD significantly increased the level of SIRT1 and reduced the levels of ACE, VCAM-1, and IL-6.Conclusions: DFD could be utilized in treating AF through a complicated mechanism, including interactions between related active compounds and targets, promoting the explanation and understanding of the molecular biological mechanism of DFD in the treatment of AF.