Study on potential common action and mechanism of Reduning Injection against SARS, MERS and COVID-19 based on network pharmacology and molecular docking technology.

Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.

In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury.

COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by network pharmacology and bioinformatics methods. The combination of the protein-protein interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment -target gene network revealed eight key target genes (VEGFA, ICAM1, IL6, CXCL8, IL1B, CCL2, IL10 and RELA). Molecular docking showed that all these eight gene-encoded proteins could be effectively bound to three major active compounds (quercetin, luteolin and kaempferol), thus becoming potential therapeutic targets. Molecular dynamics simulation also supports the binding stability of RELA-encoded protein with quercetin and luteolin. Together, our data suggest that IL6, VEGFA, and RELA could be the potential drug targets by inhibiting the NF-κB signaling pathway. Our in silico studies shed new insights into P. vulgaris and its ingredients, e.g., quercetin, as potential botanical drugs against COVID-19 AKI, and warrant further studies on efficacy and mechanisms.

Deciphering suppressive effects of Lianhua Qingwen Capsule on COVID-19 and synergistic effects of its major botanical drug pairs.

The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, ß-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.

Study on active compounds from Maxingganshi decoction for treatment of novel coronavirus pneumonia (COVID-19) based on network pharmacology and molecular docking method

Aim To explore the active compound of Maxingganshi decoction in treatment of novel coronavirus pneumonia(COVID-19). Methods With the help of TCMSP database, the chemical components and action targets of ephedra, almond, licorice, and gypsum in Maxingganshi decoction were searched, and then a C-T network, protein interaction analysis, GO functional enrichment analysis, and KEGG pathway enrichment were constructed. Analysis was performed to predict its mechanism of action. Results A total of 120 compounds in Maxingganshi decoction corresponded to 222 targets. PTGS2, ESR1, PPARG, AR, NOS2, NCOA2 acted on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, T cell receptor signaling pathways, etc. The results of molecular docking showed that the affinity of quercetin, kaempferol, glabridin and other core compounds was similar to recommended drugs in treatment of COVID-19. Conclusions The active compounds of Maxingganshi decoction can target multiple pathways to achieve the therapeutic effect of COVID-19.Copyright © 2020 Publication Centre of Anhui Medical University. All rights reserved.

AIM in Alternative Medicine

Alternative medicine (AM) is one of the medical fields that use more natural and traditional therapies for disease diagnosis and treatment, in which traditional Chinese medicine (TCM) now has been recognized as one of the main approaches of AM. As a clinical and evidencedriven discipline with long histories, AM is also heavily relied on in the utilization of big healthcare and therapeutic data for improving the capability of diagnosis and treatment. In particular, artificial intelligence (AI) has been widely adopted in AM to deliver more practical and feasible intelligent solutions for clinical operations since 1970s. This chapter summarizes the main approaches, related typical applications, and future directions of AI in AM to give related researchers a brief useful reference. We find that although AM has not been widely used in clinical practice internationally, the AI studies showed abundant experiences and technique trials in expert system, machine learning, data mining, knowledge graph, and deep learning. In addition, various types of data, such as bibliographic literatures, electronic medical records, and images were used in the related AI tasks and studies. Furthermore, during this COVID-19 pandemic era, we have witnessed the clinical effectiveness of TCM for COVID-19 treatment, which mostly was detected by real-world data mining applications. This indicates the potential opportunity of the booming of AI research and applications in various aspects (e.g., effective clinical therapy discovery and network pharmacology of AM drugs) in AM fields. © Springer Nature Switzerland AG 2022.

Exploring the Potential Mechanism of Action of Ursolic Acid against Gastric Cancer and COVID-19 using Network Pharmacology and Bioinformatics Analysis.

BACKGROUND: Patients with gastric cancer (GC) are more likely to be infected with 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the prognosis is worse. It is urgent to find effective treatment methods. OBJECTIVE: This study aimed to explore the potential targets and mechanism of ursolic acid (UA) on GC and COVID-19 by network pharmacology and bioinformatics analysis. METHODS: The online public database and weighted co-expression gene network analysis (WGCNA) were used to screen the clinical related targets of GC. COVID-19-related targets were retrieved from online public databases. Then, a clinicopathological analysis was performed on GC and COVID-19 intersection genes. Following that, the related targets of UA and the intersection targets of UA and GC/COVID-19 were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome Analysis (KEGG) pathway enrichment analyses were performed on the intersection targets. Core targets were screened using a constructed protein-protein interaction network. Finally, molecular docking and molecular dynamics simulation (MDS) of UA and core targets were performed to verify the accuracy of the prediction results. RESULTS: A total of 347 GC/COVID-19-related genes were obtained. The clinical features of GC/COVID-19 patients were revealed using clinicopathological analysis. Three potential biomarkers (TRIM25, CD59, MAPK14) associated with the clinical prognosis of GC/COVID-19 were identified. A total of 32 intersection targets of UA and GC/COVID-19 were obtained. The intersection targets were primarily enriched in FoxO, PI3K/Akt, and ErbB signaling pathways. HSP90AA1, CTNNB1, MTOR, SIRT1, MAPK1, MAPK14, PARP1, MAP2K1, HSPA8, EZH2, PTPN11, and CDK2 were identified as core targets. Molecular docking revealed that UA strongly binds to its core targets. The MDS results revealed that UA stabilizes the protein-ligand complexes of PARP1, MAPK14, and ACE2. CONCLUSION: This study found that in patients with gastric cancer and COVID-19, UA may bind to ACE2, regulate core targets such as PARP1 and MAPK14, and the PI3K/Akt signaling pathway, and participate in antiinflammatory, anti-oxidation, anti-virus, and immune regulation to exert therapeutic effects.

Multi-scale Mechanisms of Maxing Shigantang in Treating Pneumonia Based on Transcriptomic Data.

Objective: Pneumonia is an infectious inflammation of the alveoli,distal airway,and interstitium caused by bacterial,viral,and other pathogens. Maxing Shigantang,originated from Treatise On Cold Damage Diseases,is a classic prescription for treating pneumonia,with significant clinical efficacy. However,its treatment mechanism is still elusive. Method(s): In that paper,the transcriptome-based multi-scale network pharmacology was used to reveal the overall pharmacological mechanism of Maxing Shigantang in treating pneumonia from six scales of tissue,cell,pathological process,biological process,signaling pathway, and target. Result(s):At the tissue level,Maxing Shigantang mainly acted on the focal tissue of pneumonia-lung and the main inflammatory immune tissues-blood and spleen. Analysis of cell,pathological process and biological process suggested that Maxing Shigantang could treat pneumonia by reversing inflammatory and immune functions and improving cardiopulmonary and vascular injury caused by pneumonia. Analysis of signaling pathway and target showed that Maxing Shigantang regulated inflammatory immune response pathways such as "coronavirus disease-COVID-19" and "Toll-like receptor signaling pathway",and related targets such as "MAPKAPK3" and "NRG1". Conclusion(s):This paper,from molecular to tissue levels,indicated Maxing Shigantang treated pneumonia mainly by regulating inflammatory immune response and improving cardiopulmonary and vascular injury.Copyright © 2023, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Neem and Turmeric in the management of Covid Associated Mucormycosis (CAM) derived through network pharmacology.

Mucormycosis or 'Black Fungus' has been known to target immunocompromised individuals even before the emergence of COVID-19. Nevertheless, the present circumstances provide the best opening for Covid Associated Mucormycosis (CAM), as the global pandemic is engulfing a large part of human population making them immunocompromised. This drastic increase in Mucormycosis infections has to be addressed as early as possible. There is a growing tendency of relying upon herbal drugs that have minimal side effects and does not compromise our immune system. Recently, the concept of network pharmacology has grabbed the attention of modern science, especially advanced medical sciences. This is a new discipline that can use computational power to systematically catalogue the molecular interactions between botanical formulations and the human body. In this study, Neem and Turmeric was considered as the target plants and an attempt was made to reveal various aspects through which phytocompounds derived from them may effectively manage CAM menace. We have taken a step-by-step approach for identifying the target proteins and ligands associated with Mucormycosis treatment. Functional network analysis and Molecular docking approaches were applied to validate our findings. Quercetin derived from both Neem and Turmeric was found to be one of the main phytocompounds working against Mucormycosis. Along with that, Caffeic acid, Curcumin, Kaempferol, Tetrahydrocurcumin and Myricetin also play a pivotal role in fighting against Black-Fungus. A thorough analysis of our result suggested a triple-front attack on the fungal pathogens and the approaches are necrosis inhibition, iron chelation and immuno-boosting.Communicated by Ramaswamy H. Sarma.

Study on prescription medication mode and mechanism of traditional Chinese medicine in the treatment of noncritical COVID-19 based on data mining

Background: As of 2023, coronavirus disease 2019 (COVID-19) is still spreading globally. Therefore, we aim to integrate non-critical COVID-19 high-frequency and high-targeting Chinese medicines to provide a reference for clinical prescriptions to improve COVID-19-related symptoms. Materials and methods: The information on non-critical COVID-19 high-frequency Chinese medicines in the diagnosis and treatment of COVID-19 was obtained by the TCM inheritance support platform. Using network pharmacology and molecular docking technology, high-targeting Chinese medicines with good docking activity with COVID-19 receptors angiotensin-converting enzyme-II (ACE2), 3CLpro and tyrosine-protein kinase receptor UFO (AXL) were obtained. A new prescription for non-critical COVID-19 was established by integrating high-frequency and high-targeting Chinese medicines. Rats with acute lung injury induced by lipopolysaccharide were used as the experimental model. The histopathological changes in the lungs of rats in each group were observed by hematoxylin-eosin staining. The lung coefficient of rats was measured. The levels of IL-6, TNF-a, and IL-1ß in serum were detected by enzyme-linked immunosorbent assay. The mRNA and protein levels of ACE2 and AXL in lung tissue were detected by real-time quantitative polymerase chain reaction and western blot. Results: Through data mining, it was found that there were 39 high-frequency traditional Chinese medicines for non-critical COVID-19 in the diagnosis and treatment guidelines. According to network pharmacology and molecular docking, 30 highly targeted traditional Chinese drugs for COVID-19 were found. The new prescriptions for non-critical COVID-19 were comprehensively obtained, including Glycyrrhizae Radix, Ephedra Herba, Amygdalus Communis Vas, Gypsum Fibrosum, Descurainiae Semen, Atractylodes Lancea, Scutellariae Radix, Amomum Tsao-Ko Crevostet, Forsythiae Fructus, Pogostemon cablin, Magnolia Officinalis. Compared with the LPS-induced lung injury model group, the medium dose of the new prescription group had significantly alleviated pathological changes in lung tissue, decreased lung coefficient, decreased contents of IL-6, TNF-a and IL-1ß, and increased mRNA and protein expression of ACE2 and AXL (P < 0.05). Conclusion: Based on data mining, network pharmacology and molecular docking technology, the new prescription for non-critical COVID-19 established by this method has an anti-inflammatory effect on rats with acute lung injury induced by lipopolysaccharide and can provide a reference for clinicians to alleviate the symptoms related to non-critical COVID-19. [ FROM AUTHOR] Copyright of Traditional Medicine Research is the property of TMR Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Multi-scale Mechanisms of Maxing Shigantang in Treating Pneumonia Based on Transcriptomic Data

Objective： Pneumonia is an infectious inflammation of the alveoli，distal airway，and interstitium caused by bacterial，viral，and other pathogens. Maxing Shigantang，originated from Treatise On Cold Damage Diseases，is a classic prescription for treating pneumonia，with significant clinical efficacy. However，its treatment mechanism is still elusive. Method： In that paper，the transcriptome-based multi-scale network pharmacology was used to reveal the overall pharmacological mechanism of Maxing Shigantang in treating pneumonia from six scales of tissue，cell，pathological process，biological process，signaling pathway， and target. Result：At the tissue level，Maxing Shigantang mainly acted on the focal tissue of pneumonia-lung and the main inflammatory immune tissues-blood and spleen. Analysis of cell，pathological process and biological process suggested that Maxing Shigantang could treat pneumonia by reversing inflammatory and immune functions and improving cardiopulmonary and vascular injury caused by pneumonia. Analysis of signaling pathway and target showed that Maxing Shigantang regulated inflammatory immune response pathways such as "coronavirus disease-COVID-19" and "Toll-like receptor signaling pathway"，and related targets such as "MAPKAPK3" and "NRG1". Conclusion：This paper，from molecular to tissue levels，indicated Maxing Shigantang treated pneumonia mainly by regulating inflammatory immune response and improving cardiopulmonary and vascular injury. © 2023, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Network pharmacological analysis of Epimedium and Morinda officinalis for COVID-2019 with deficiency of lung and kidney

Objective To explore the potential mechanism of Epimedium and Morinda officinalis in the treatment of Corona Virus Disease 2019 (COVID-19) with deficiency of lung and kidney by network pharmacology. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to search the compounds in Epimedium and Morinda, and the active components and targets were screened. Uniprot database was used for standardization, and the genes corresponding to the targets were searched. GeneCards database was used to obtain the targets of COVID-19 with deficiency of lung and kidney. The drug-compound-target network was constructed by the software of Cycloscape3. 7. 2, protein-protein interaction (PPI) network was constructed and analyzed by using Search Tool for the Retrieval of Interacting Genes (STRING) database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) path analysis were conducted by the software of Funrich 3. 1. 3. Results Epimedium and Morinda officinalis had 41 effective targets in the treatment of COVID-19. There were 2 831 targets associated with COVID-19 with deficiency of lung and kidney, and the key targets were IL6, VEGFA,CASP3, HIF1A, CCND1 9 EGFR etc. A total of 802 GO enrichment entries and 125 KEGG pathways were obtained, mainly involving PI3K-Akt signaling pathway, lipid and atherosclerosis, Kaposi sarcoma-associated herpesvirus infection, microRNAs in cancer, human cytomegalovirus infection, Epstein-Barr virus infection, etc. Conclusion The treatment of COVID-19 with deficiency of lung and kidney is the result of multi-target and multi-channel interaction, and it can be used as an adjuvant therapy for COVID-19 with deficiency of lung and kidney, which provides certain theoretical basis for expanding the clinical application of Chuankezhi injection. (English) [ABSTRACT FROM AUTHOR] 目的 运用网络药理学方法探讨淫羊藿-巴戟天治疗新型冠状病毒感染(新冠感染)肺肾两虚型 的潜在作用机制。方法 通过中药系统药理学数据库与分析平台检索淫羊藿、巴戟天含有的化合物,筛选其活 性成分及其作用靶点;运用 Uniprot数据库进行标准化处理,查询靶点对应的基因;通过 GeneCards数据库获 取新冠感染肺肾两虚型的相关靶标;采用 Cytoscape3.7.2软件构建药物-化合物-靶点网络,STRING 数据库进 行蛋白质相互作用(PPI)网络的构建与分析;通过 Funrich3.1.3软件进行基因本体(GO)富集分析和京都基因 与基因组百科全书(KEGG)通路分析。结果 获得淫羊藿-巴戟天治疗新冠感染的共41个有效靶点,新冠感染 肺肾两虚型相关靶点2831个,关键靶点有白细胞介素-6(IL-6)、血管内皮生长因子 A(VEGFA)、胱天蛋白酶3 (CASP3)、缺氧诱导因子1α(HIF1α)、细胞周期蛋白 D1(CCND1)、人类表皮生长因子受体(EGFR)等;获得802 个 GO 富集条目和125条 KEGG 通路,主要涉及磷酸肌醇-3激酶/蛋白激酶 B 信号通路、脂质核动脉粥样硬 化、卡波西氏肉瘤疱疹病毒感染、肿瘤相关 mRNA、人巨细胞病毒感染、艾巴氏病毒感染等。结论 淫羊藿-巴 戟天治疗新冠感染肺肾两虚型是多靶点、多途径相互作用的结果,可作为新冠感染肺肾两虚型的辅助治疗方 法,为扩展喘可治注射液的临床应用提供一定理论依据。 (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Journal of Modern Medicine & Health is the property of Journal of Modern Medicine & Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A method of mechanism analysis about a traditional chinese medicine prescription on a disease based on PageRank algorithm and network pharmacology

Network pharmacology is a method to study the mechanism of a Traditional Chinese Medicine (TCM) prescription on a disease. However, most articles using network pharmacology to study the mechanism did not combine the weight information of herbs, the weight information of targets of disease, and the interaction information between targets together. We propose a method, network pharmacology combined with two iterations of PageRank algorithm, to make use of these information. It takes prescription-disease system as a whole, calculates PageRank score of targets in the prescription-disease system, which means an importance in the system, and the score is used to rank the analysis results of GO and KEGG pathway which help us to analyze the mechanism of a prescription on a disease. At last, we use two prescription-disease pairs which have been proved effectiveness in clinical trials: Qingfei Paidu Decoction on COVID-19, and FuFang DanShen Diwan on Coronary Heart Disease, and find that the results of our method are consistent with some results of clinical trials.Copyright © 2021

Network pharmacology research of mechanism of Maxing Shigan Decoction in treating COVID-19

Background: The COVID-19 has a huge negative impact on people's health. Traditional Chinese Medicine (TCM) has a good effect on viral pneumonia. It is of great practical significance to study its pharmacology. Methods: The ingredients and targets of each herb in Maxing Shigan Decoction which obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the related targets of COVID-19 were screened by GeneCards database based on the network pharmacology. Venn was used to analyze the intersection target between active ingredients and diseases. Cytoscape software was used to construct an active ingredient-disease target network. The protein-protein interaction network was constructed by STRING database and Cytohubba was used to screen out the key targets. Gene Ontology (GO) functional enrichment analysis and KEGG pathway analysis were performed by DAVID database. Results: In this study, a total of 134 active ingredients and 229 related targets, 198 targets of COVID-19 and 48 common targets of drug-disease were chosen. Enrichment items and pathways were obtained through GO and KEGG pathway analysis. The predicted active ingredients were quercetin, kaempferol, luteolin, naringenin, glycyrol, and the key targets involved IL6, MAPK3, MAPK8, CASP3, IL10, etc. The results showed that the active ingredients of Maxing Shigan Decoction acted on multiple targets which played roles in the treatment of COVID-19 by regulating inflammation, immune system and other pathways. Conclusions: The main contribution of this paper is to use data to mine the principles of the treatment of COVID-19 from the pharmacology of these prescriptions, and the results can be provided theoretical reference for medical workers. © The Author (s) 2023. Published by Higher Education Press.

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

Identification of phytochemical compounds of Fagopyrum dibotrys and their targets by metabolomics, network pharmacology and molecular docking studies.

Acute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys, among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys, and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys, 89 these phytochemicals's potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys. Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys, such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys. We also fully developed the medicinal value of F. dibotrys' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine.

An integrated approach of high-performance liquid chromatography-mass spectrometry-based chemical profiling, network pharmacology, and molecular docking to reveal the potential mechanisms of Qishen Gubiao granules for treating coronavirus disease 2019.

Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.

DiDang decoction improves mitochondrial function and lipid metabolism via the HIF-1 signaling pathway to treat atherosclerosis and hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: DiDang Decoction (DDD) is a traditional classical prescription that has been used to treat atherosclerosis (AS) and hyperlipidemia (HLP) in China. Nevertheless, the underlying mechanism of DDD remains unclear. AIM OF THE STUDY: To validate the mechanism of DDD in AS and HLP based on network pharmacology and in vitro experiments. MATERIALS AND METHODS: The chemical components of DDD were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database and literature mining, and the disease targets of AS and HLP were obtained from the Gencards, OMIM, and DisGeNET databases. The intersection genes were imported into the STRING database to construct protein-protein interaction (PPI) network, and the DAVID database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Combined with the results of KEGG pathway analysis, the HIF-1 signaling pathway was selected for further in vitro experiments. RESULTS: The results showed that network pharmacology predicted 112 targets related to DDD treatment of AS and HLP, and the top 10 related pathways are: Lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, Chemical carcinogenesis - receptor activation, Pathways in cancer, Proteoglycans in cancer, Fluid shear stress and atherosclerosis, HIF-1 signaling pathway, Alcoholic liver disease, PPAR signaling pathway, and Coronavirus disease-COVID-19. In vitro experiments showed that DDD effectively reduced lipid accumulation in FFA-treated L02 cells; DDD attenuated mitochondrial damage and reduced ROS content; DDD inhibited ferroptosis and apoptosis; DDD up-regulated the expression of HIF-1α, Glutathione Peroxidase 4(GPX4), and Bcl2 proteins, and down-regulated expression of Bax protein. CONCLUSION: DDD exerts therapeutic effects on AS and HLP through multiple targets and pathways, and improves mitochondrial function, reduces ROS content, inhibits ferroptosis and apoptosis by activating the HIF-1 signaling pathway, which provides reliable theoretical and experimental support for DDD treatment of AS and HLP.

Network-based drug repurposing for the treatment of COVID-19 patients in different clinical stages.

In the severe acute respiratory coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to develop effective treatments. Through a network-based drug repurposing approach, several effective drug candidates are identified for treating COVID-19 patients in different clinical stages. The proposed approach takes advantage of computational prediction methods by integrating publicly available clinical transcriptome and experimental data. We identify 51 drugs that regulate proteins interacted with SARS-CoV-2 protein through biological pathways against COVID-19, some of which have been experimented in clinical trials. Among the repurposed drug candidates, lovastatin leads to differential gene expression in clinical transcriptome for mild COVID-19 patients, and estradiol cypionate mainly regulates hormone-related biological functions to treat severe COVID-19 patients. Multi-target mechanisms of drug candidates are also explored. Erlotinib targets the viral protein interacted with cytokine and cytokine receptors to affect SARS-CoV-2 attachment and invasion. Lovastatin and testosterone block the angiotensin system to suppress the SARS-CoV-2 infection. In summary, our study has identified effective drug candidates against COVID-19 for patients in different clinical stages and provides comprehensive understanding of potential drug mechanisms.

The medicinal value of tea drinking in the management of COVID-19.

Corona Virus Disease 2019 (COVID-19) is presently the largest international public health event, individuals infected by the virus not only have symptoms such as fever, dry cough, and lung infection at the time of onset, but also possibly have sequelae in the cardiovascular system, respiratory system, nervous system, mental health and other aspects. However, numerous studies have depicted that the active ingredients in tea show good antiviral effects and can treat various diseases by regulating multiple pathways, and the therapeutic effects are associated with the categories of chemical components in tea. In this review, the differences in the content of key active ingredients in different types of tea are summarized. In addition, we also highlighted their effects on COVID-19 and connected sequelae, further demonstrating the possibility of developing a formulation for the prevention and treatment of COVID-19 and its sequelae through tea extracts. We have a tendency to suggest forestalling and treating COVID-19 and its sequelae through scientific tea drinking.

Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology.

Purpose: Aimed to identify the anti-uterine corpus endometrial carcinoma (UCEC) function and characterize the mechanism of quercetin in the treatment of patients infected with COVID-19 via integrated in silico analysis. Methods: The Cancer Genome Atlas and Genotype Tissue Expression databases were applied to obtain differentially expressed genes of UCEC and non-tumor tissue. Several in silico methods such as network pharmacology, functional enrichment analysis, Cox regression analyses, somatic mutation analysis, immune infiltration and molecular docking were used to investigate and analysis the biological targets, functions and mechanisms of anti-UCEC/COVID-19 of quercetin. Multiple methods such as CCK8 assay, Transwell assay and western blotting were performed to test proliferation, migration, and protein level of UCEC (HEC-1 and Ishikawa) cells. Results: Functional analysis disclosed that quercetin against UCEC/COVID-19 mainly by 'biological regulation', 'response to stimulus', and 'regulation of cellular process'. Then, regression analyses indicated that 9 prognostic genes (including ANPEP, OAS1, SCGB1A1, HLA-A, NPPB, FGB, CCL2, TLR4, and SERPINE1) might play important roles in quercetin for treating UCEC/COVID-19. Molecular docking analysis revealed that the protein products of 9 prognostic genes were the important anti-UCEC/COVID-19 biological targets of quercetin. Meanwhile, the proliferation and migration of UCEC cells were inhibited by quercetin. Moreover, after treatment with quercetin, the protein level of ubiquitination-related gene ISG15 was decreased in UCEC cells in vitro. Conclusions: Taken together, this study provides new treatment option for UCEC patients infected with COVID-19. Quercetin may work by reducing the expression of ISG15 and participating in ubiquitination-related pathways.