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Based on the international concern about COVID-19 and pulmonary diseases, the number of cases of lung injury caused by COVID-19 pneumonia and its complications has increased dramatically in recent years, and the complexity of the situation makes the combination of single drugs a major problem in respiratory diseases. Therefore, it would be feasible to replace single drug combinations with compounded formulations for the treatment of a diverse array of pulmonary diseases. At the same time, the visualization of the chemical composition of herbal formulations and the study of molecular interactions to reveal the mechanism of action will be of practical significance. This paper introduced the therapeutic mechanisms of the traditional Chinese medicine formula Three Agents White Powder. Three major pulmonary diseases, COVID-19, pulmonary fibrosis, and lung abscess, were investigated using molecular docking and network pharmacology approaches. Mainly using TCMSP, DAVID, STRING, Genecard database screening, and autodock molecular docking methods, this paper verified that this drug applies its healing benefits to pulmonary diseases through multiple components, multiple targets, and multiple pathways, and illustrated the effectiveness of this formula in the adjuvant treatment of extensive pulmonary diseases. © 2023 SPIE.
ABSTRACT
Introduction: The National Administration of Traditional Chinese Medicine of the People's Republic of China (NATCM) and the State Administration of Traditional Chinese medicine (TCM) advocated a combination therapy of TCM and anti-viral drugs for novel coronavirus pneumonia (NCP) to improve the efficacy of clinical treatment. Methods: Forty-six patients diagnosed with NCP were sequentially divided into intent-to-treat population: the experimental group (combination of FuXi-Tiandi-Wuxing Decoction and anti-viral drugs; n = 23) and the control group (anti-viral drugs only) (n = 23). The two groups were compared in terms of duration of fever, cough symptom score, fatigue, appetite, dyspnea, out-of-bed activities, chest computer tomography (CT) recovery, virological clearance, average length of hospital stay, and clinical effective rate of drug. After 6 days of observation, patients from the control group were divided into as-treated population: experimental subgroup (n = 14) to obtain clinical benefit and control subgroup (n = 9). Results: There was a significant improvement in the duration of fever (1.087 ± 0.288 vs 4.304 ± 2.490), cough (0.437 ± 0.589 vs 2.435 ± 0.662; P < 0.05), chest CT evaluation (82.6% vs 43.4%; P < 0.05), and virological clearance (60.8% vs 8.7%; P < 0.05) in patients of the experimental group compared with patients in the control group. Further observation in as-treated population reported that cough (0.742 ± 0.463 vs 1.862 ± 0.347; P < 0.05) and fatigue (78.5% vs 33.3%; P < 0.05) were significantly relieved after adding FuXi-Tiandi-Wuxing Decoction to the existing treatment. Conclusion: An early treatment with combination therapy of FuXi-Tiandi-Wuxing Decoction and anti-viral drugs significantly relieves the clinical symptoms of NCP, shows improvement in chest CT scan, improves virological clearance, shortens average length of hospital stay, and reduces the risk of severe illness. The effect of FuXi-Tiandi-Wuxing Decoction in NCP may be clinically important and require further consideration.
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Objective To explore the application pattern and mechanism of medicine and food homologous traditional Chinese medicine (TCM) against modern viral diseases. Methods The method of literature mining was applied based on the characteristics of modern viral diseases, combining with ancient books and modern prescriptions for the prevention and treatment of viral diseases to build a relevant prescription database. Then SPSS and R language were used to analyze the high-frequency medicine and food homologous TCM and high confidence medicine and food homologous prescriptions in these prescriptions, and cluster analysis was carried out. The antiviral characteristic active ingredients of high-frequency medicinal and food homologous TCN were identified and analyzed, and the action mechanism of active ingredients against modern viral diseases was evaluate by network pharmacology. Results In the prevention and treatment of modern viral diseases, Gancao (Glycyrrhizae Radix et Rhizoma)-Chenpi (Citri Reticulatae Pericarpium)-Fuling (Poria) had the highest confidence, Glycyrrhizae Radix et Rhizoma-Jiegeng (Platycodonis Radix) had the highest support. At the same time, the prescriptions were clustered and analyzed to obtain Jinyinhua (Lonicerae Japonicae Flos)-Huangqi (Astragali Radix)-Huoxiang (Agastache rugosa), Glycyrrhizae Radix et Rhizoma-Xingren (Armeniacae Semen Amarum)-Poria-Platycodonis Radix-Citri Reticulatae Pericarpium, Ganjiang (Zingiberis Rhizoma)-Renshen (Ginseng Radix et Rhizoma), Zisu (Perilla frutescens)-Gegen (Puerariae Lobatae Radix), Lugen (Phragmitis Rhizoma)-Sangye (Mori Folium), Shengjiang (Zingiberis Rhizoma Recens)-Dazao (Jujubae Fructus) clustering new prescription. The core action targets of EGFR, CASP3, VEGFA, STAT3, MMP9, HSP90AA1, mTOR, PTGS2, MMP2, TLR4, MAPK14, etc were identified. The action mechanism involved human cytomegalovirus infection, coronavirus disease-coronavirus disease 2019 (COVID-19), etc. The core action pathway were phosphatidylinositol-3/kinase protein kinase B (PI3K/Akt) signal pathway, mitogen activated protein kinase (MAPK) signal pathway, interleukin-17 (IL-17) signal pathway, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signal pathway, etc. Conclusion Through data mining, six new prescriptions for preventing and controlling modern viral diseases were obtained, and the mechanism of action was preliminarily discussed, which provided some reference for the research and development of medicine and food homologous TCM prescriptions for the prevention and treatment of viral epidemics and related health products.
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Objective: To investigate the possible mechanism of Platycodonis Radix-Licorice drug pair in the intervention of COVID-19 by using network pharmacology and molecular docking technique. Methods The database TCMSP was retrieved for the chemical constituents and targets of Platycodonis Radix-Licorice drug pair. Coronavirus disease targets were screened by the Gene Cards, OMIM,TTD, PharmGkb and DrugBank database. Cytoscape 3.7.2 software was used to construct the drug-component-target network. The PPI(protein-protein interaction) network was obtained by drug-disease intersection targets, and the core genes were found through CytoNCA plug-in. Meanwhile, GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) pathway analysis were performed by using Bioconductor database to predict the mechanism. AutoDock Tools 1.5.6 software was used to simulate the molecular docking of the main active ingredients with the novel coronavirus key binding site protein [SARS-CoV-2 main protease(severe acute respiratory syndrome coronavirus 2 main protease, Mpro) and ACE2(angiotensin converting enzyme 2)]. Results A total of 7 active ingredients of Platycodonis Radix,92 active ingredients of Licorice,2766 drug targets, and 674 disease targets were obtained, and 67 drug-disease common targets were excavated. The key targets involved RELA,STAT1,MAPK3,TP53,MAPK1,MAPK8,STAT3,MAPK14,IL1 B and TNF by the database STRING and CytoNCA plug-in.Go enrichment analysis showed that the main functions of Platycodonis Radix-Licorice drug pair on the intervention of COVID-19 were antioxidant reaction, cell respond to chemical stress, regulation of apoptotic signaling pathways, reaction to lipopolysaccharides and reaction to bacteria-derived molecules, etc.. KEGG pathways involved Coronavirus disease-COVID-19 pathway, IL-17 signaling pathway and so on, were mainly associated with immune response, inflammation-related pathways, inhibition of viral infection, and other inhibition of cancer. The molecular docking results showed that glepidotin A,quercetin, licochalcone a and luteolin had good binding ability with Mpro and ACE2. Conclusion Platycodonis Radix-Licorice drug pair act on SARS-CoV-2 through multiple components, multiple targets, and multiple channel combination. And the main active ingredients have a fine binding ability with Mpro and ACE2. The method can provide theoretical support for the possibility of traditional Chinese medicine(TCM) against COVID-19.
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Platycodon grandiflorus (Jacq.) A. DC. (Campanulaceae) is commonly known as a balloon flower whose rhizomes have been widely utilized in traditional Chinese medicine (TCM) and in various Japanese prescriptions for the treatment of respiratory diseases, diabetes, and inflammatory disorders. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) global pandemic requires priming of the virus's spike (S) protein by cleavage of the S proteins by a multi-domain type II transmembrane serine protease, transmembrane protease serine 2 (TMPRSS2) to gain entry into the host cell. The current research aims at the screening of active phytocompounds of P. grandiflorus as potential inhibitors of cellular TMPRSS2 using molecular docking and molecular dynamics simulations approach. In silico toxicity analyses show that out of a total of 34 phytocompounds selected for the study, 12 compounds obey Lipinski's rule of five and have favourable pharmacokinetic properties. The top three lead molecules identified here were Apigenin, Luteolin and Ferulic acid which exhibited binding energies of -7.47 kcal/mol, -6.8 kcal/mol and -6.62 kcal/mol respectively with corresponding inhibition constants of 3.33 µM, 10.39 µM and 13.95 µM. The complexes between the lead molecules and the receptor were held by hydrogen bond interactions with key residues such as Gly383, Gly385, Glu389, Lys390, Asp435, Ser436, Ser441, Cys465 and Lys467, and hydrophobic interactions with surrounding residues. The stability of the protein-ligand complexes was evaluated during 100 ns molecular dynamics (MD) simulation by analysing key geometric properties such as RMSD, RMSF, radius of gyration, total solvent accessible surface area and the number of hydrogen bonds. The binding free energies analysis using MD simulations revealed that the compounds and TMPRSS2 have favourable thermodynamic interactions, which are primarily driven by van der Waals forces. As a result, the selected bioactive phytochemicals from P. grandiflorus that target the cellular TMPRSS2 could offer an alternative treatment option against SARS-CoV-2 infections.
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Adjuvants are common vaccine components. Novel adjuvants may improve the protective immunity conferred by vaccines against poultry diseases. Here, a less-hemolytic saponin, platycodin D (PD), isolated from the root of Platycodon grandiflorum was investigated as a potential alternative adjuvant. PD was tested as an adjuvant in the infectious bronchitis (IB) vaccine, because the existing IB vaccine has often failed to induce effective immune responses. The adjuvant activity of PD in conjunction with IB vaccine was evaluated in this study. Compared to control treatment, PD treatment significantly increased the proliferation of chicken peripheral blood mononuclear cells, concentration of interferon-γ in culture supernatants, and anti-IB antibody titer. In chickens pre-challenged with the Mass 41 infectious bronchitis virus (IBV), PD administration resulted in fewer and less severe clinical signs, lower mortality rate, and higher protection compared to control treatment. Histopathological examination showed that the lungs and kidneys of PD-treated chickens displayed fewer pathological lesions than those of control chickens. Our results also demonstrated that this new vaccine adjuvant improved chicken humoral and cellular immune responses without any side effects. Hence, our findings suggest that PD might serve as an effective adjuvant in IBV vaccines.