scholarly journals Mechanism of protective effect of xuan-bai-cheng-qi decoction on LPS-induced acute lung injury based on an integrated network pharmacology and RNA-sequencing approach

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huahe Zhu ◽  
Shun Wang ◽  
Cong Shan ◽  
Xiaoqian Li ◽  
Bo Tan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Rna Sequencing ◽  
Target Genes ◽  
Mammalian Target Of Rapamycin ◽  
Network Pharmacology ◽  
Protective Mechanism ◽  
Rna Seq ◽  
Active Components ◽  
Integrated Network

AbstractXuan-bai-cheng-qi decoction (XCD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat a variety of respiratory diseases in China, especially to seriously infectious diseases such as acute lung injury (ALI). Due to the complexity of the chemical constituent, however, the underlying pharmacological mechanism of action of XCD is still unclear. To explore its protective mechanism on ALI, firstly, a network pharmacology experiment was conducted to construct a component-target network of XCD, which identified 46 active components and 280 predicted target genes. Then, RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) between ALI model rats treated with and without XCD and 753 DEGs were found. By overlapping the target genes identified using network pharmacology and DEGs using RNA-seq, and subsequent protein–protein interaction (PPI) network analysis, 6 kernel targets such as vascular epidermal growth factor (VEGF), mammalian target of rapamycin (mTOR), AKT1, hypoxia-inducible factor-1α (HIF-1α), and phosphoinositide 3-kinase (PI3K) and gene of phosphate and tension homology deleted on chromsome ten (PTEN) were screened out to be closely relevant to ALI treatment. Verification experiments in the LPS-induced ALI model rats showed that XCD could alleviate lung tissue pathological injury through attenuating proinflammatory cytokines release such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Meanwhile, both the mRNA and protein expression levels of PI3K, mTOR, HIF-1α, and VEGF in the lung tissues were down-regulated with XCD treatment. Therefore, the regulations of XCD on PI3K/mTOR/HIF-1α/VEGF signaling pathway was probably a crucial mechanism involved in the protective mechanism of XCD on ALI treatment.

scholarly journals Mechanism of Protective Effect of Xuan-Bai-Cheng-Gi Decoction on LPS-Induced Acute Lung Injury Based on an Integrated Network Pharmacology and RNA-Sequencing Approach

2020 ◽  
Author(s):  
Huahe Zhu ◽  
Shun Wang ◽  
Cong Shan ◽  
Xiaoqian Li ◽  
Bo Tan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Rna Sequencing ◽  
Target Genes ◽  
Mammalian Target Of Rapamycin ◽  
Network Pharmacology ◽  
Protective Mechanism ◽  
Rna Seq ◽  
Active Components ◽  
Integrated Network

Abstract Xuan-bai-cheng-qi decoction (XCD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat a variety of respiratory diseases in China, especially to seriously infectious diseases such as acute lung injury (ALI). Due to the complexity of the chemical constituent, however, the underlying pharmacological mechanism of action of XCD is still unclear. To explore its protective mechanism on ALI, firstly, a network pharmacology experiment was conducted to construct a component-target network of XCD, which identified 46 active components and 280 predicted target genes. Then, RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) between ALI model rats treated with and without XCD and 753 DEGs were found. By overlapping the target genes identified using network pharmacology and DEGs using RNA-seq, and subsequent protein-protein interaction (PPI) network analysis, 6 kernel targets such as vascular epidermal growth factor (VEGF), mammalian target of rapamycin (mTOR), AKT1, hypoxia-inducible factor-1α (HIF-1α), and phosphoinositide 3-kinase (PI3K) and gene of phosphate and tension homology deleted on chromsome ten (PTEN) were screened out to be closely relevant to ALI treatment. Validation experiments in the LPS-induced ALI model rats showed that XCD could alleviate lung tissue pathological injury through attenuating proinflammatory cytokines release such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Meanwhile, both the mRNA and protein expression levels of PI3K, mTOR, HIF-1α, and VEGF in the lung tissues were downregulated with XCD treatment. Therefore, the regulations of XCD on PI3K/mTOR/HIF-1α/VEGF signaling pathway was probably a crucial mechanism involved in the protective mechanism of XCD on ALI treatment.

scholarly journals Network Pharmacology-Based Investigation of Protective Mechanism of Aster tataricus on Lipopolysaccharide-Induced Acute Lung Injury

2019 ◽  
Vol 20 (3) ◽  
pp. 543 ◽  
Author(s):  
Yijun Chen ◽  
Jiaojiao Dong ◽  
Jie Liu ◽  
Wenjuan Xu ◽  
Ziyi Wei ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cells ◽  
Network Pharmacology ◽  
Protective Mechanism ◽  
Lung Pathology ◽  
Vascular Endothelial ◽  
Relative Peak Area ◽  
Effective Components ◽  
The Common

Acute lung injury (ALI) is a common clinical condition that badly influences people’s health. Recent studies indicated that Aster tataricus (RA) had potential effects on ALI, but the effective components and their mechanism is not clear. In this study, we found that the Fraction-75 eluted from RA extract could significantly protect the lipopolysaccharide (LPS)-induced ALI in mice, including alleviating the severity of lung pathology, attenuating the pulmonary edema, and reducing the release of inflammatory cells. Further ingredient analyses demonstrated that there were mainly 16 components in it, among which 10 components were collected according to their relative peak area and oral bioavailability. Next, the components-disease targets network suggested that the candidate components had extensive associations with 49 known therapeutic targets of ALI, among which 31 targets could be regulated by more than one component. Herein, GO functional and pathway analysis revealed that the common targets were associated with four biological processes, including the inflammatory response to stimulus, cellular process, chemokine biosynthetic process and immune system process. Furthermore, the ELISA validation indicated that the candidate components in RA extract may protect the LPS-induced ALI mainly through inhibiting the release of inflammatory cytokines and promoting the repair of vascular endothelial.

scholarly journals EGCG promotes PRKCA expression to alleviate LPS-induced acute lung injury and inflammatory response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mian Wang ◽  
Hua Zhong ◽  
Xian Zhang ◽  
Xin Huang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Weight Ratio ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Protective Mechanism ◽  
High Morbidity ◽  
Inflammatory Factor ◽  
Egcg Treatment

AbstractAcute lung injury (ALI), which could be induced by multiple factors such as lipopolysaccharide (LPS), refer to clinical symptoms of acute respiratory failure, commonly with high morbidity and mortality. Reportedly, active ingredients from green tea have anti-inflammatory and anticancer properties, including epigallocatechin-3-gallate (EGCG). In the present study, protein kinase C alpha (PRKCA) is involved in EGCG protection against LPS-induced inflammation and ALI. EGCG treatment attenuated LPS-stimulated ALI in mice as manifested as improved lung injury scores, decreased total cell amounts, neutrophil amounts and macrophage amounts, inhibited the activity of MPO, decreased wet-to-dry weight ratio of lung tissues, and inhibited release of inflammatory cytokines TNF-α, IL-1β, and IL-6. PRKCA mRNA and protein expression showed to be dramatically decreased by LPS treatment while reversed by EGCG treatment. Within LPS-stimulated ALI mice, PRKCA silencing further aggravated, while PRKCA overexpression attenuated LPS-stimulated inflammation and ALI through MAPK signaling pathway. PRKCA silencing attenuated EGCG protection. Within LPS-induced RAW 264.7 macrophages, EGCG could induce PRKCA expression. Single EGCG treatment or Lv-PRKCA infection attenuated LPS-induced increases in inflammatory factors; PRKCA silencing could reverse the suppressive effects of EGCG upon LPS-stimulated inflammatory factor release. In conclusion, EGCG pretreatment inhibits LPS-induced ALI in mice. The protective mechanism might be associated with the inhibitory effects of PRKCA on proinflammatory cytokine release via macrophages and MAPK signaling pathway.

Molecular Mechanism of The Effect of Huanglian Jiedu Decoction On Ulcerative Colitis Based On Network Pharmacology And Molecular Docking

2021 ◽  
Author(s):  
Jing Yang ◽  
Chao-Tao Tang ◽  
Ruiri Jin ◽  
Bixia Liu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Signal Pathway ◽  
Intestinal Barrier Function ◽  
Network Pharmacology ◽  
Bioactive Components ◽  
Ppi Network ◽  
Active Components

Abstract Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC by means of network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are considered to be very important to PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had good affinity with Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.

Discussing the Mechanism of Dahuang Huanglian Xiexin Decoction in the Treatment of Type 2 Diabetes Mellitus via Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Xi Cen ◽  
Yan Wang ◽  
LeiLei Zhang ◽  
XiaoXiao Xue ◽  
Yan Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Potential Mechanism ◽  
Active Components ◽  
The Core ◽  
Core Genes

Abstract BackgroundType 2 diabetes mellitus (T2DM) is regarded as Pi Dan disease in traditional Chinese medicine (TCM). Dahuang Huanglian Xiexin Decoction (DHXD), a classical TCM formula, has been used for treating Pi Dan disease in clinic, its pharmacological mechanism has not been elucidated. MethodsThis study used network pharmacological analysis and molecular docking approach to explore the mechanism of DHXD on T2DM. Firstly, the compounds in DHXD were obtained from TCMSP and TCMID databases, the potential targets were determined based on TCMSP and UniProt databases. Next, Genecards, Digenet and UniProt databases were used to identify the targets of T2DM. Then, the protein-protein interaction (PPI) network was established with overlapping genes of T2DM and compounds, and the core targets in the network were identified and analyzed. Then, the David database was used for GO and KEGG enrichment analysis. Finally, the target genes were selected and the molecular docking was completed by Autodock software to observe the binding level of active components with target genes.ResultsA total of 397 related components and 128 overlapping genes were identified. After enrichment analysis, it was found that HIF-1, TNF, IL-17 and other signaling pathways, as well as DNA transcription, gene expression, apoptosis and other cellular biological processes had the strongest correlation with the treatment of T2DM by DHXD, and most of them occurred in the extracellular space, plasma membrane and other places, which were related to enzyme binding and protein binding. In addition, 42 core genes of DHXD, such as VEGFA, TP53 and MAPK1, were considered as potential therapeutic targets, indicating the potential mechanism of DHXD on T2DM. Finally, the results of molecular docking showed that HIF-1 pathway had strong correlation with the target genes INSR and GLUT4, quercetin and berberine had the strongest binding power with them respectively.ConclusionThis study summarized the main components of DHXD in the treatment of T2DM, identified the core genes and pathways, and systematically analyzed the interaction of related targets, trying to lay the foundation for clarifying the potential mechanism of DHXD on T2DM, so as to carry out further research in the future.

scholarly journals Lipopolysaccharide Inhibits Alpha Epithelial Sodium Channel Expression via MiR-124-5p in Alveolar Type 2  Epithelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yan Ding ◽  
Yong Cui ◽  
Zhiyu Zhou ◽  
Yapeng Hou ◽  
Xining Pang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Sodium Channel ◽  
Target Genes ◽  
Cell Model ◽  
Epithelial Sodium Channel ◽  
Alveolar Epithelial Cells ◽  
Luciferase Assay ◽  
Alveolar Type

Mesenchymal stem cells (MSCs) have been a potential strategy in the pretreatment of pulmonary diseases, while the mechanisms of MSCs-conditioned medium (MSCs-CM) involved with microRNAs on the regulation of lung ion transport are seldom reported. We investigated the role of miR-124-5p in lipopolysaccharide-involved epithelial sodium channel (ENaC) dysfunction and explored the potential target of miR-124-5p. We observed the lower expression of miR-124-5p after the administration of MSCs-CM, and the overexpression or inhibition of miR-124-5p regulated epithelial sodium channel α-subunit (α-ENaC) expression at protein levels in mouse alveolar type 2 epithelial (AT2) cells. We confirmed that α-ENaC is one of the target genes of miR-124-5p through dual luciferase assay and Ussing chamber assay revealed that miR-124-5p inhibited amiloride-sensitive currents associated with ENaC activity in intact H441 monolayers. Our results demonstrate that miR-124-5p can decrease the expression and function of α-ENaC in alveolar epithelial cells by targeting the 3′-UTR. The involvement of MSCs-CM in lipopolysaccharide-induced acute lung injury cell model could be related to the downregulation of miR-124-5p on α-ENaC, which may provide a new target for the treatment of acute lung injury.

scholarly journals Mechanism of 1,25(OH)2D3 in the Treatment of Acute Lung Injury Based on UHPLC/Q-TOF MS-Based Metabolomics and Network Pharmacology

2020 ◽  
Author(s):  
Xuan Shi ◽  
Yuanli Chen ◽  
Yiguo Zhang ◽  
Xiaohong Jin ◽  
Huanping Zhou ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Regulation Mechanism ◽  
High Morbidity ◽  
Potential Mechanism ◽  
Serum Samples ◽  
Inflammatory Infiltration ◽  
Tof Ms

Abstract Background: Sepsis-induced acute lung injury (ALI), a high morbidity and mortality disease, still has no effective therapies. 1,25(OH)2D3 is one of the indispensable nutrients in our body. The regulation mechanism of 1,25(OH)2D3 in inflammation has been recognized gradually. Network pharmacology was used wildly to broaden the understanding of diseases and advance drug discovery. In this study, we used network pharmacology and metabolomics to generate the potential mechanism of 1,25(OH)2D3 on acute lung injury.Methods: We used metabolomics and network pharmacology to elucidate the therapeutic mechanism of 1,25(OH)2D3 on acute lung injury. Serum samples, collected from mice with LPS-induced acute lung injury, were detected by UHPLC/Q-TOF MS to evaluate the differential metabolites from multiple metabolic pathways. Meanwhile, the H＆E staining, ELISA and QPCR were used to estimate the efficacy of 1,25(OH)2D3 on acute lung injury. Results: The results of animal experiments showed that 1,25(OH)2D3 could mitigate severe pulmonary edema and inflammatory infiltration caused by LPS, and the treatment of 1,25(OH)2D3 reduced the levels of inflammatory cytokines, interacted 25 related proteins and TNF signaling pathway, Toll-like receptor signaling pathway, PI3K-Akt signaling pathway.Conclusions: The integrated methods coupled with UHPLC/Q-TOF MS and network pharmacology provided a new way to study the potential mechanism of 1,25(OH)2D3 on acute lung injury, which may provide a possible solution for patients with clinical acute lung injury.

Sign in / Sign up

Export Citation Format

Share Document