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Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis.

ABSTRACT: Pulmonary fibrosis (PF) is one of the pathologic changes in COVID-19 patients in convalescence, and it is also a potential long-term sequela in severe COVID-19 patients. Qimai Feiluoping decoction (QM) is a traditional Chinese medicine formula recommended in the Chinese national medical program for COVID-19 convalescent patients, and PF is one of its indications. Through clinical observation, QM was found to improve the clinical symptoms and pulmonary function and reduce the degree of PF of COVID-19 convalescent patients. To further explore the pharmacological mechanisms and possible active components of QM in anti-PF effect, UHPLC/Q-TOF-MS was used to analyze the composition of the QM extract and the active components that can be absorbed into the blood, leading to the identification of 56 chemical compounds and 10 active components. Then, network pharmacology was used to predict the potential mechanisms and targets of QM; it predicted that QM exerts its anti-PF effects via the regulation of the epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) degradation, and TGF-β signaling pathway. Finally, TGF-β1-induced A549 cells were used to verify and explore the pharmacological effects of QM and found that QM could inhibit the proliferation of TGF-β1-induced A549 cells, attenuate EMT, and promote ECM degradation by inhibiting the TGF-β/Smad3 pathway.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8678473 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis.

Yang Yingying Y Ding Lu L Bao Tingting T Li Yaxin Y Ma Jing J Li Qingwei Q Gao Zezheng Z Song Siyu S Wang Jing J Zhao Jiachao J Wang Ziyuan Z Zhao Daqing D Li Xiangyan X Wang Zeyu Z Zhao Linhua L Tong Xiaolin X

Frontiers in pharmacology 20211203

Pulmonary fibrosis (PF) is one of the pathologic changes in COVID-19 patients in convalescence, and it is also a potential long-term sequela in severe COVID-19 patients. Qimai Feiluoping decoction (QM) is a traditional Chinese medicine formula recommended in the Chinese national medical program for COVID-19 convalescent patients, and PF is one of its indications. Through clinical observation, QM was found to improve the clinical symptoms and pulmonary function and reduce the degree of PF of COVI ...[more]

PMID: 34925028

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Project description:Qing-Jin-Hua-Tan-Decoction (QJHTD), a classic famous Chinese ancient prescription, has been used for treatment of pulmonary diseases since Ming Dynasty. A total of 22 prototype compounds of QJHTD absorbed into rat blood were chosen as candidates for the pharmacological network analysis and molecular docking. The targets from the intersection of compound target and ALI disease targets were used for GO and KEGG enrichment analyses. Molecular docking was adopted to further verify the interactions between 22 components and the top 20 targets with higher degree values in the component-target-pathway network. In vitro experiments were performed to verify the results of network pharmacology using SPR experiments, Western blot experiments, and the PMA-induced neutrophils to produce neutrophil extracellular trap (NET) model. The compound-target-pathway network includes 176 targets and 20 signaling pathways in which the degree of MAPK14, CDK2, EGFR, F2, SRC, and AKT1 is higher than that of other targets and which may be potential disease targets. The biological processes in QJHTD for ALI mainly included protein phosphorylation, response to wounding, response to bacterium, regulation of inflammatory response, and so on. KEGG enrichment analyses revealed multiple signaling pathways, including lipid and atherosclerosis, HIF-1 signaling pathway, renin-angiotensin system, and neutrophil extracellular trap formation. The molecular docking results showed that baicalin, oroxylin A-7-glucuronide, hispidulin-7-O-β-D-glucuronide, wogonoside, baicalein, wogonin, tianshic acid, and mangiferin can be combined with most of the targets, which might be the core components of QJHTD in treatment of ALI. Direct binding ability of baicalein, wogonin, and baicalin to thrombin protein was all micromolar, and their KD values were 11.92 μM, 1.303 μM, and 1.146 μM, respectively, revealed by SPR experiments, and QJHTD could inhibit Src phosphorylation in LPS-activated neutrophils by Western blot experiments. The experimental results of PMA-induced neutrophils to produce NETs indicated that QJHTD could inhibit the production of NETs. This study revealed the active compounds, effective targets, and potential pharmacological mechanisms of QJHTD acting on ALI.

Project description:PurposeThe network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM).MethodsActive ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis.ResultsA total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1.ConclusionThis study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.

Project description:BackgroundYeju Jiangya decoction (CIF) is an herbal formula from traditional Chinese medicine (TCM) for the treatment of hypertension.Materials and methodsBased on the analysis of network pharmacology, combined with in animal experiments, the network pharmacology was used to explore the potential proteins and mechanisms of CIF against hypertension. The bioactive compounds of CIF were screened by using the platform, and the targets of hypertension and CIF were collected. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) core targets were carried out, and the useful proteins were found by molecular docking technology. Finally, we used N-nitro-L-arginine (L-NNA) induced hypertension model rats to confirm the effect and mechanism of CIF on hypertension.Results14 bioactive compounds of CIF passed the virtual screening criteria, and 178 overlapping targets were identified as core targets of CIF against hypertension. The CIF-related target network with 178 nodes and 344 edges is constructed. The topological results show that quercetin and luteolin are the key components in the network. The key targets NOS3 (nitric oxide synthase 3) and NOS2 (nitric oxide synthase 2) were screened by the protein-protein interaction network. The analysis of target protein pathway enrichment showed that the accumulation pathway is related to the vascular structure of CIF regulation of hypertension. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. On the other hand, NOS3 has an important relationship with the composition of blood vessels. Furthermore, the animal experiment indicated that after the L-NNA-induced hypertension rat model was established, CIF intervention was given by gavage for 3 weeks, and it can decrease serum concentrations of endothelin-1 (ET-1) and thromboxane B2 (TXB2), increase the expression of nitric oxide (NO) and prostacyclin 2 (PGI2), and improve renal, cardiac, and aortic lesions. At the same time, it can reduce blood pressure and shorten vertigo time. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC-α1), guanylyl cyclase-alpha 2 (GC-α2), and protein kinase CGMP-dependent 1 (PRKG1). These results suggest that CIF may play an antihypertensive role by inhibiting the activation of the NOS3/PRKG1 pathway.ConclusionsThe results of this study indicate that CIF has the ability to improve target organs, protect endothelial function, and reduce blood pressure and that CIF might be a potential therapeutic drug for the prevention of hypertension. It provides new insight into hypertension and the potential biological basis and mechanism for CIF clinical research.

Project description:BackgroundTo explore the mechanism of compound Hongginshen decoction in improving pulmonary fibrosis based on network pharmacology.MethodsThe active components and targets of ginseng and Salvia miltiorrhiza were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The chemical components of Rhodiola, Ophiopogon japonicus, and Dendrobium were screened using the Traditional Chinese Medicine Integrated Database (TCMID), and the target compounds were predicted by the Swisstargets method. The related target genes of pulmonary fiber (PF) were screened by the Genecards database and the National Center of Biotechnology Information (NCBI) database. The protein-protein interaction network was drawn using the string database and Cytoscape software, and the network topology was analyzed. Then, using R3.6.3 software, biological processes, molecular function, cell component enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out on the common targets of drugs and diseases. The network diagram of the "traditional Chinese medicine composition disease target" of Compound Hongginshen Decoction was constructed and analyzed with the software of Cytoscape 3.6.1.ResultsWe identified 159 active components and 2820 targets in Compound Hongginshen Decoction, and 2680 targets in pulmonary fibrosis. A total of 343 common targets were obtained by the intersection of drug targets and disease targets. protein-protein interaction protein interaction network analysis showed that PIK3CA, PIK3R1, MAPK1, SRC, AKT1, and so on may be the core targets of the compound Hongjingshen recipe in the treatment of pulmonary fibrosis. Gene Ontology (GO) enrichment analysis identified 3463 items, and KEGG pathway enrichment analysis identified 181 related signaling pathways, including the PI3K-Akt signaling pathway, HCMV pathway, Hb pathway, PGs pathway, and KSHV signaling pathway.ConclusionCompound Hongginshen Decoction has the characteristics of a multichannel and multitargeted effect in the treatment of pulmonary fibrosis. Radix Ophiopogonis and Dendrobium officinale play a key role in the treatment of pulmonary fibrosis. The whole compound prescription may play a therapeutic role by affecting cell metabolism, being anti-inflammatory, regulating the immune system, promoting angiogenesis, and improving anaerobic metabolism.

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Dataset Information

Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis.

Publications

Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis.

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