An evidence update on the protective mechanism of tangeretin against neuroinflammation based on network pharmacology prediction and transcriptomic analysis

2021 ◽  
pp. 174094
Author(s):  
Shuo Lv ◽  
Qiyang Chen ◽  
Zhenqing Li ◽  
Zhiqin Zhou
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huahe Zhu ◽  
Shun Wang ◽  
Cong Shan ◽  
Xiaoqian Li ◽  
Bo Tan ◽  
...  

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.


2020 ◽  
Author(s):  
Huahe Zhu ◽  
Shun Wang ◽  
Cong Shan ◽  
Xiaoqian Li ◽  
Bo Tan ◽  
...  

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.


2020 ◽  
Vol 48 (5) ◽  
pp. 441-449
Author(s):  
Xiaobo Xuan ◽  
Ziyan Sun ◽  
Chenhuan Yu ◽  
Jian Chen ◽  
Mei Chen ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 338 ◽  
Author(s):  
Rong Wu ◽  
Shu Dong ◽  
Fei-Fei Cai ◽  
Xiao-Le Chen ◽  
Meng-Die Yang ◽  
...  

Fuzheng huayu formula (FZHY), an antifibrotic traditional Chinese medicine, is frequently used for the treatment of liver fibrosis. In this study, network analysis, transcriptomic analysis, assays of cell apoptosis, viability and protein expression were used for investigating the effects and mechanisms of compounds derived from FZHY on hepatic parenchymal cell (HPC) protection and hepatic stellate cell activation. Network pharmacology analysis found that 6 major compounds and 39 potential targets were important network nodes. Our analysis predicted that the active compounds of FZHY, including hederagenin, luteolin and tanshinone IIA inhibited cell apoptosis (p < 0.05), increased PI3K expression and reduced cleaved caspase 3 expression and the Bax/Bcl-w ratio (p < 0.05) in L02 cells that had apoptosis induced by TNF-α. Few significant changes caused by FZHY, hederagenin, luteolin and tanshinone IIA were observed in hepatic stellate Lx2 cells upon TGF-β1 induction. These data suggest that FZHY is active against liver fibrosis, protects hepatic parenchymal cells from apoptosis, and recovers liver function, possibly through the effects of its active compounds hederagenin, luteolin and tanshinone IIA and is involved in the inhibition of apoptosis in HPCs, possibly through regulating the PI3K, ERK, cleaved caspase 3 and Bax/Bcl-w levels.


2021 ◽  
Vol 11 ◽  
Author(s):  
Fengxia Wu ◽  
Cai Chen ◽  
Fulai Peng

Background: The prevalence of Helicobacter pylori infection (HPI) is still high around the world, which induces gastric diseases, such as gastric cancer (GC). The epidemiological investigation showed that there was an association between HPI and asthma (AST). Coptidis rhizoma (CR) has been reported as an herbal medicine with anti-inflammatory and anti-bacterial effects.Purpose: The present study was aimed to investigate the protective mechanism of HPI on AST and its adverse effects on the development of GC. Coptis chinensis was used to neutralize the damage of HPI in GC and to hopefully intensify certain protective pathways for AST.Method: The information about HPI was obtained from the public database Comparative Toxicogenomics Database (CTD). The related targets in AST and GC were obtained from the public database GeneCards. The ingredients of CR were obtained from the public database Traditional Chinese Medicine Systems Pharmacology (TCMSP). The network pharmacology including gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking were utilized. Protein–protein interaction was constructed to analyze the functional link of target genes. The molecular docking was employed to study the potential effects of active ingredients from CR on key target genes.Result: The top 10 key targets of HPI for AST were CXCL9, CX3CL1, CCL20, CCL4, PF4, CCL27, C5AR1, PPBP, KNG1, and ADORA1. The GO biological process involved mainly leukocyte migration, which responded to bacterium. The (R)-canadine and quercetin were selected from C. chinensis, which were employed to explore if they inhibited the HPI synchronously and protect against AST. The targets of (R)-canadine were SLC6A4 and OPRM1. For ingredient quercetin, the targets were AKR1B1 and VCAM1.Conclusion: CXCL9 and VCAM1 were the common targets of AST and HPI, which might be one of the imported targets of HPI for AST. Quercetin could be an effective ingredient to suppress HPI and help prevent AST.


2019 ◽  
Vol 20 (3) ◽  
pp. 543 ◽  
Author(s):  
Yijun Chen ◽  
Jiaojiao Dong ◽  
Jie Liu ◽  
Wenjuan Xu ◽  
Ziyi Wei ◽  
...  

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.


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