scholarly journals Network Pharmacology Elucidates the Anti-Inflammatory Mechanisms of QingFeiPaiDu Decoction for Treatment of COVID-19

2021 ◽  
Vol 000 (000) ◽  
pp. 000-000
Author(s):  
Yan Liu ◽  
Lewen Xiong ◽  
Yanyu Wang ◽  
Mengxiong Luo ◽  
Longfei Zhang ◽  
...  
2020 ◽  
Vol 48 (07) ◽  
pp. 1693-1713
Author(s):  
Zhichen Pu ◽  
Yanhao Liu ◽  
Chao Li ◽  
Moadi Xu ◽  
Haitang Xie ◽  
...  

Ulcerative colitis is a chronic and recurrent inflammatory bowel disease mediated by immune response. Geniposide is the main active ingredient extracted from Gardenia jasminoides, which has been suggested to exert excellent efficacy on inflammatory disease. Herein, in this study, we aimed to uncover the systematic understanding of the mechanism and effects of geniposide in ameliorating inflammatory responses in colitis. In brief, the TCMSP server and GEO DataSets were used to analyze the systematic understanding of the mechanism and effects of geniposide in ameliorating inflammatory responses in colitis. Dextran Sulfate Sodium (DSS)-induced acute colitis of mice were administered with 25–100[Formula: see text]mg/kg of geniposide for 7 days by gavage. Lipopolysaccharide (LPS)-induced Bone Marrow Derived Macrophage (BMDM) cell or RAW264.7 cell models were treated with 20, 50 and 100[Formula: see text][Formula: see text]M of geniposide for 4[Formula: see text]h. Myeloperoxidase (MPO) activity and Interleukin-1[Formula: see text] (IL-1[Formula: see text] levels were measured using MPO activity kits and IL-1[Formula: see text] levels enzyme-linked immunosorbent assay (ELISA) kits, respectively. Additionally, Western blot was used to determine the relevant protein expression. As a result, Geniposide could ameliorate inflammatory responses and prevent colitis in DSS-induced acute colitis of mice by activating AMP-activated protein kinase (AMPK)/Transcription 1 (Sirt1) dependent signaling via the suppression of nod-like receptor protein 3 (NLRP3) inflammasome. Geniposide attenuated macrophage differentiation in DSS-induced acute colitis of mice. Geniposide suppressed NLRP3 inflammasome and induced AMPK/Sirt1 signaling in LPS-induced BMDM cell or RAW264.7 cell models. In mechanism studies, the inhibition of AMPK/Sirt1 attenuated the anti-inflammatory effects of geniposide in colitis. The activation of NLRP3 attenuated the anti-inflammatory effects of geniposide in colitis. Taken together, our results demonstrated that geniposide ameliorated inflammatory responses in colitis vai the suppression of NLRP3 inflammasome in macrophages by AMPK/Sirt1-dependent signaling.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yizhe Cui ◽  
Qiuju Wang ◽  
Renxu Chang ◽  
Ahmad Aboragah ◽  
Juan J. Loor ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is associated with high morbidity and mortality. Pogostemon cablin (Blanco) Benth/Huo Xiang (HX) is a perennial herb with unique anti-oxidant and anti-inflammatory properties, and thus, can positively affect liver function. In this study, we used network pharmacology to predict the potential mechanism of HX on NAFLD. Pharmacological experiments were used to verify the effect of HX on the functions of NAFLD. Network pharmacology identified nine components that interacted with 82 NAFLD-related targets, revealing four target genes: TNF, IL6, TP53, and AKT1. HX prevents the development and progression of NAFLD through different pathways and targets with quercetin-regulated lipid metabolism, anti-inflammatory, and anti-oxidant pathways playing an essential role in the treatment of NAFLD. Compared with feeding HFD, HX significantly attenuated lipid accumulation in vivo with mice and also in vitro with mouse liver cells. A high dose of HX decreased hepatocyte lipid accumulation and the abundance of SREBF1 and FASN. Validation experiments revealed that HX inhibited the activation of NF-κB/IκB signaling and decreased the release and levels of pro-inflammatory factors (TNF-α and IL-6). These data suggest that HX can attenuate abnormal lipid metabolic responses and enhance antioxidant mechanisms. Thus, the pharmacological effects from plants used in traditional Chinese medicine are achievde through a multi-level response.


2020 ◽  
Author(s):  
Junfang Feng ◽  
Ou Chen ◽  
Yibiao Wang

Abstract Background: Network pharmacological methods were used to predict the anti-inflammatory targets and related pathways of rhein in the treatment of asthma, and to elucidate its mechanism of action. In addition, we validated the anti-inflammatory effects of rhein in HBE cells. Methods: The corresponding targets of rhein were obtained from the TCMSP 2.3, and molecular docking was also performed. A network of predicted rhein targets was established and analysed with Cytoscape 3.7.1. The anti-inflammatory targets in the TTD database were searched to build a PPI network, which was merged with the ingredient-target network to screen anti-inflammatory targets associated with rhein. A network of anti-inflammatory rhein targets during the in vivo treatment of asthma was constructed to screen the anti-inflammatory targets related to asthma. KEGG enrichment analysis was performed with the Enrichr database and Cytoscape 3.7.1. The expression levels of proteins in the MAPK/NF-κB signalling pathway were assessed by western blot analysis. Results: Altogether, 17 targets were obtained. Epidermal active growth factor receptor (EGFR), E-selecting (E-SELE), macrophage migration inhibitory factor (MIF), and mitogen-activated protein kinase 14 (MAPK14) might be important anti-inflammatory targets of rhein during asthma treatment. We selected the MAPK signalling pathway to determine the anti-inflammatory effects of rhein. Conclusion: The anti-inflammatory mechanism of the treatment of asthma with rhein may be related to MAPK14, EGFR, E-SELE and MIF as well as their signalling pathways. To prevent the exacerbation of asthma, instead of targeting a single pathway or a single target, all these targets and their signalling pathways should be controlled holistically. Rhein may reduce inflammation by inhibiting the MAPK/NF-κB pathway.


2021 ◽  
Author(s):  
Bo Jia ◽  
Xi-Yue Tan ◽  
Xing-Long Liu ◽  
Xin-Yun Li

Abstract Ulcerative colitis (UC), one forms of chronic inflammatory bowel disease (IBD), is characterized by recurrent inflammation, and Renshen Baidu Powder (RSBDP) is often used as a traditional Chinese medicine prescription for treating of UC, but the pharmacological mechanisms remains unclear. This research aims to explore the mechanisms of RSBDP in the treatment of UC based on network pharmacology. Through multiple databases collected the compounds and targets, and constructed the network. The crossover genes enrichment analysis were performed by protein-protein interaction (PPI) construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, 181 compounds and 266 targets were obtained. Potential candidate ingredients mainly include phytosterols, flavonoids, and coumarins, all of which have anti-inflammatory activities. GO and KEGG enrichment analysis suggested that RSBDP have anti-inflammatory and immunomodulatory effects. The effect of RSBDP on UC might be achieved by regulating the balance of cytokines (i.e., IL-6, TNF, IL-1) and the downstream mediators (i.e., STAT1, STAT3) in the immune system. And inflammation-, immune- and hypoxic-related pathways, like TNF, Toll-like receptors and HIF-1 signaling pathway. These results provide a theoretical basis for studying the effective substances of RSBDP in the treatment of UC and their mechanism of action for further research.


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