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1.
J Ethnopharmacol ; 299: 115674, 2022 Dec 05.
Article in English | MEDLINE | ID: covidwho-2069311

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. AIM OF THE STUDY: Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. MATERIALS AND METHODS: The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. RESULTS: The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. CONCLUSIONS: The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research.


Subject(s)
Acute Lung Injury , Antitussive Agents , Drugs, Chinese Herbal , Immunomodulating Agents , Acute Lung Injury/drug therapy , Analgesics/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antitussive Agents/therapeutic use , Cytokines/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Essential/therapeutic use , Immunomodulating Agents/pharmacology , Immunomodulating Agents/therapeutic use , Mice , Network Pharmacology/methods , Rats , Receptors, Antigen, T-Cell/therapeutic use
2.
J Integr Med ; 20(6): 477-487, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2041962

ABSTRACT

Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Humans , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Network Pharmacology , Medicine, Chinese Traditional/methods , Treatment Outcome
3.
Molecules ; 27(17)2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2010213

ABSTRACT

Since the outbreak of the COVID-19 pandemic, traditional Chinese medicine has played an important role in the treatment process. Furthermore, the discovery of artemisinin in Artemisia annua has reduced the incidence of malaria all over the world. Therefore, it is becoming urgent and important to establish a novel method of conducting systematic research on Chinese herbal medicine, improving the medicinal utilization value of traditional Chinese medicine and bringing great benefits to human health all over the world. Fructus Malvae, a kind of Chinese herbal medicine which has been recorded in the "Chinese Pharmacopoeia" (2020 edition), refers to the dry, ripe fruits of Malva verticillata L. Recently, some studies have shown that Fructus Malvae exhibits some special pharmacological activities; for example, it has diuretic, anti-diabetes, antioxidant and anti-tumor properties, and it alleviates hair loss. Furthermore, according to the reports, the active ingredients separated and identified from Fructus Malvae contain some very novel compounds such as nortangeretin-8-O-ß-d-glucuronopyranoside and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride, which could be screened as important candidate compounds for diabetes- or tumor-treatment drugs, respectively. Therefore, in this research, we take Fructus Malvae as an example and systematically summarize the chemical constituents and pharmacological activity research progress of it. This review will be helpful in promoting the development and application of Fructus Malvae and will also provide an example for other investigations of traditional Chinese medicine.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Fruit , Humans , Medicine, Chinese Traditional , Pandemics
4.
Front Cell Infect Microbiol ; 12: 965273, 2022.
Article in English | MEDLINE | ID: covidwho-2005850

ABSTRACT

Purpose: The Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (XFBD) significantly improved patient's clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism. Methods: We screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration. Results: XFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy. Conclusion: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , SARS-CoV-2 , COVID-19/drug therapy , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Molecular Dynamics Simulation , NLR Family, Pyrin Domain-Containing 3 Protein , SARS-CoV-2/drug effects
5.
Sci Rep ; 12(1): 14296, 2022 08 22.
Article in English | MEDLINE | ID: covidwho-2000922

ABSTRACT

Honghua (Carthami flos) and Xihonghua (Croci stigma) have been used in anti-COVID-19 as Traditional Chinese Medicine, but the mechanism is unclear. In this study, we applied network pharmacology by analysis of active compounds and compound-targets networks, enzyme kinetics assay, signaling pathway analysis and investigated the potential mechanisms of anti-COVID-19. We found that both herbs act on signaling including kinases, response to inflammation and virus. Moreover, crocin likely has an antiviral effect due to its high affinity towards the human ACE2 receptor by simulation. The extract of Honghua and Xihonghua exhibited nanozyme/herbzyme activity of alkaline phosphatase, with distinct fluorescence. Thus, our data suggest the great potential of Honghua in the development of anti-COVID-19 agents.


Subject(s)
COVID-19 , Carthamus tinctorius , Drugs, Chinese Herbal , COVID-19/drug therapy , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation
6.
Phytomedicine ; 104: 154324, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2000662

ABSTRACT

BACKGROUND: COVID-19 highly caused contagious infections and massive deaths worldwide as well as unprecedentedly disrupting global economies and societies, and the urgent development of new antiviral medications are required. Medicinal herbs are promising resources for the discovery of prophylactic candidate against COVID-19. Considerable amounts of experimental efforts have been made on vaccines and direct-acting antiviral agents (DAAs), but neither of them was fast and fully developed. PURPOSE: This study examined the computational approaches that have played a significant role in drug discovery and development against COVID-19, and these computational methods and tools will be helpful for the discovery of lead compounds from phytochemicals and understanding the molecular mechanism of action of TCM in the prevention and control of the other diseases. METHODS: A search conducting in scientific databases (PubMed, Science Direct, ResearchGate, Google Scholar, and Web of Science) found a total of 2172 articles, which were retrieved via web interface of the following websites. After applying some inclusion and exclusion criteria and full-text screening, only 292 articles were collected as eligible articles. RESULTS: In this review, we highlight three main categories of computational approaches including structure-based, knowledge-mining (artificial intelligence) and network-based approaches. The most commonly used database, molecular docking tool, and MD simulation software include TCMSP, AutoDock Vina, and GROMACS, respectively. Network-based approaches were mainly provided to help readers understanding the complex mechanisms of multiple TCM ingredients, targets, diseases, and networks. CONCLUSION: Computational approaches have been broadly applied to the research of phytochemicals and TCM against COVID-19, and played a significant role in drug discovery and development in terms of the financial and time saving.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Hepatitis C, Chronic , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Artificial Intelligence , COVID-19/drug therapy , China , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Hepatitis C, Chronic/drug therapy , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Phytochemicals/pharmacology
7.
Phytomedicine ; 102: 154153, 2022 Jul 20.
Article in English | MEDLINE | ID: covidwho-1977720

ABSTRACT

BACKGROUND: The cytokine storm (CS) triggered by coronavirus disease 2019 (COVID-19) has caused serious harm to health of humanity and huge economic burden to the world, and there is a lack of effective methods to treat this complication. PURPOSE: In this research, we used network pharmacology and molecular docking to reveal the interaction mechanism in the glycyrrhetinic acid (GA) for the treatment of CS, and validated the effect of GA intervention CS by experiments. STUDY DESIGN: First, we screened corresponding target of GA and CS from online databases, and obtained the action target genes through the Venn diagram. Then, protein-protein interaction (PPI) network, Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the action target genes were acquired by R language to predict its mechanism. Next, molecular docking was performed on core targets. Finally, experiments in which GA intervened in lipopolysaccharide (LPS)-induced CS were implemented. RESULTS: 84 action target genes were obtained from online database. The PPI network of target genes showed that TNF, IL6, MAPK3, PTGS2, ESR1 and PPARG were considered as the core genes. The results of GO and KEGG showed that action target genes were closely related to inflammatory and immune related signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, Human cytomegalovirus infection, PPAR signaling pathway and so on. Molecule docking results prompted that GA had fine affinity with IL6 and TNF proteins. Finally, in vivo and in vitro experimental results showed that GA could significantly inhibit LPS-induced CS. CONCLUSION: GA has a potential inhibitory effect on CS, which is worthy of further exploration.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Glycyrrhetinic Acid , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Drugs, Chinese Herbal/pharmacology , Glycyrrhetinic Acid/pharmacology , Glycyrrhetinic Acid/therapeutic use , Humans , Interleukin-6 , Lipopolysaccharides , Molecular Docking Simulation
8.
J Integr Med ; 20(6): 561-574, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1966871

ABSTRACT

OBJECTIVE: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology. METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets. RESULTS: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase. CONCLUSION: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Humans , COVID-19/drug therapy , Molecular Docking Simulation , Ligands , Network Pharmacology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/chemistry , Medicine, Chinese Traditional
9.
Viruses ; 14(7)2022 Jul 21.
Article in English | MEDLINE | ID: covidwho-1957451

ABSTRACT

Used in Asian countries, including China, Japan, and Thailand, Houttuynia cordata Thumb (H. cordata; Saururaceae, HC) is a traditional herbal medicine that possesses favorable antiviral properties. As a potent folk therapy used to treat pulmonary infections, further research is required to fully elucidate the mechanisms of its pharmacological activities and explore its therapeutic potential for treating pneumonia caused by SARS-CoV-2. This study explores the pharmacological mechanism of HC on pneumonia using a network pharmacological approach combined with reprocessing expression profiling by high-throughput sequencing to demonstrate the therapeutic mechanisms of HC for treating pneumonia at a systemic level. The integration of these analyses suggested that target factors are involved in four signaling pathways, including PI3K-Akt, Jak-STAT, MAPK, and NF-kB. Molecular docking and molecular dynamics simulation were applied to verify these results, indicating a stable combination between four metabolites (Afzelin, Apigenin, Kaempferol, Quercetin) and six targets (DPP4, ELANE, HSP90AA1, IL6, MAPK1, SERPINE1). These natural metabolites have also been reported to bind with ACE2 and 3CLpro of SARS-CoV-2, respectively. The data suggest that HC exerts collective therapeutic effects against pneumonia caused by SARS-CoV-2 and provides a theoretical basis for further study of the active drug-like ingredients and mechanism of HC in treating pneumonia.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Houttuynia , Pneumonia , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Humans , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , SARS-CoV-2 , Thailand
10.
Phytother Res ; 36(11): 4210-4229, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1935726

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In China, the Acacia catechu (AC)-Scutellariae Radix (SR) formula has been widely used for pulmonary infection in clinical practice for several centuries. However, the potential role and mechanisms of this formula against COVID-19 remains unclear. The present study was designed to dissect the active ingredients, molecular targets, and the therapeutic mechanisms of AC-SR formula in the treatment of COVID-19 based on a systems pharmacology strategy integrated by ADME screening, target prediction, network analysis, GO and KEGG enrichment analysis, molecular docking, and molecular dynamic (MD) simulations. Finally, Quercetin, Fisetin(1-), kaempferol, Wogonin, Beta-sitosterol, Baicalein, Skullcapflavone II, Stigmasterol were primarily screened to be the potentially effective active ingredients against COVID-19. The hub-proteins were TP53, JUN, ESR1, MAPK1, Akt1, HSP90AA1, TNF, IL-6, SRC, and RELA. The potential mechanisms of AC-SR formula in the treatment of COVID-19 were the TNF signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway, etc. Furthermore, virtual docking revealed that baicalein, (+)-catechin and fisetin(1-) exhibited high affinity to SARS-CoV-2 3CLpro, which has validated by the FRET-based enzymatic inhibitory assays with the IC50 of 11.3, 23.8, and 44.1 µM, respectively. And also, a concentration-dependent inhibition of baicalein, quercetin and (+)-catechin against SARS-CoV-2 ACE2 was observed with the IC50 of 138.2, 141.3, and 348.4 µM, respectively. These findings suggested AC-SR formula exerted therapeutic effects involving "multi-compounds and multi-targets." It might be working through directly inhibiting the virus, improving immune function, and reducing the inflammatory in response to anti-COVID-19. Ultimately, this study would provide new perspective for discovering potential drugs and mechanisms against COVID-19.


Subject(s)
Acacia , COVID-19 , Catechin , Drugs, Chinese Herbal , Humans , COVID-19/drug therapy , SARS-CoV-2 , Scutellaria baicalensis , Molecular Docking Simulation , Quercetin/pharmacology , Quercetin/therapeutic use , Network Pharmacology , Phosphatidylinositol 3-Kinases , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional
11.
Zhongguo Zhong Yao Za Zhi ; 47(13): 3409-3424, 2022 Jul.
Article in Chinese | MEDLINE | ID: covidwho-1939525

ABSTRACT

The Chinese medicinal herb Mahuang is herbaceous stem of Ephedra sinica, E. intermedia, or E. equisetina(Family, Ephedraceae). In China, Mahuang has been used, all the way over a millennium, as a key component herb of many herbal medicines for management of epidemics of acute respiratory illness and is also used in officially recommended herbal medicines for COVID-19. Mahuang is the first-line medicinal herb for cold and wheezing and also an effective diuretic herb for edema. However, Mahuang can also exert significant adverse effects. The key to safety and effectiveness is rational and precise use of the herb. In this review article, we comprehensively summarize chemical composition of Mahuang and associated differences in pharmacognosy, pharmacodynamics and pharmacokinetics of Mahuang compounds, along with the adverse effects of Mahuang compounds and products. Based on full understanding of how Mahuang is used in Chinese traditional medicine, systematic research on Mahuang in line with contemporary standards of pharmaceutical sciences will facilitate promoting Chinese herbal medicines to become more efficient in management of epidemic illnesses, such as COVID-19. To this end, we recommend research on Mahuang of two aspects, i.e., pharmacological investigation for its multicompound-involved therapeutic effects and toxicological investigation for clinical manifestation of the adverse effects, chemicals responsible for the adverse effects, and conditions for safe use of the herb and the herb-containing medicines.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Ephedra sinica , Ephedra , COVID-19/drug therapy , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Ephedra sinica/chemistry , Ephedrine/chemistry , Humans , Plants
12.
Phytomedicine ; 100: 154083, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1895370

ABSTRACT

BACKGROUND: The high incidence of thrombotic events is one of the clinical characteristics of coronavirus disease of 2019 (COVID-19), due to a hyperinflammatory response caused by the virus. Gegen Qinlian Pills (GQP) is a Traditional Chinese Medicine that is included in the Chinese Pharmacopoeia and played an important role in the clinical fight against COVID-19. Although GQP has shown the potential to treat thrombosis, there is no relevant research on its treatment of thrombosis so far. HYPOTHESIS: We hypothesized that GQP may be capable inhibit inflammation-induced thrombosis. STUDY DESIGN: We tested our hypothesis in a carrageenan-induced thrombosis mouse model in vivo and lipopolysaccharide (LPS)-induced human endothelial cells (HUVECs) in vitro. METHODS: We used a carrageenan-induced mouse thrombus model to confirm the inhibitory effect of GQP on inflammation-induced thrombus. In vitro, studies in human umbilical vein endothelial cells (HUVECs) and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of GQP and determine the main components, targets, and pathways of GQP, respectively. RESULTS: Oral administration of 227.5 mg/kg, 445 mg/kg and 910 mg/kg of GQP significantly inhibited thrombi in the lung, liver, and tail and augmented tail blood flow of carrageenan-induced mice with reduced plasma tumor necrosis factor α (TNF-α) and diminished expression of high mobility group box 1 (HMGB1) in lung tissues. GQP ethanol extract (1, 2, or 5 µg/ml) also reduced the adhesion of platelets to LPS stimulated HUVECs. The TNF-α and the expression of HMGB1, nuclear factor kappa B (NF-κB), and NLR family pyrin domain containing 3 (NLRP3) in LPS stimulated HUVECs were also attenuated. Moreover, we analyzed the components of GQP and inferred the main targets, biological processes, and pathways of GQP in the treatment of inflammation-induced thrombosis through network pharmacology. CONCLUSION: Overall, we demonstrated that GQP could reduce inflammation-induced thrombosis by inhibiting HMGB1/NFκB/NLRP3 signaling and provided an accurate explanation for the multi-target, multi-function mechanism of GQP in the treatment of thromboinflammation, and provides a reference for the clinical usage of GQP.


Subject(s)
Drugs, Chinese Herbal , HMGB1 Protein , Thrombosis , Animals , Carrageenan , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides , Mice , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Thrombosis/chemically induced , Thrombosis/drug therapy , Tumor Necrosis Factor-alpha/metabolism
13.
Biomed Pharmacother ; 152: 113254, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1889242

ABSTRACT

Sang Xing decoction (SXD) is a typical prescription for treating "warm dryness" in traditional Chinese medicine (TCM), which is equivalent to respiratory diseases such as acute bronchitis in modern medicine. However, its mechanism of action remains unclear. In this study, the representative components of SXD were characterized using liquid chromatography-tandem mass spectrometry (LC-MS). The key targets, signaling pathways, and metabolic pathways associated with SXD in the treatment of acute bronchitis were identified via network prediction and metabolomics. A rat model of acute bronchitis was also established using mixed smoke, systematic in vivo experiments such as histopathological analyses, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, immunohistochemistry and western blotting were conducted to evaluate the network prediction results. An in-depth analysis of the targeted quantitative results was performed using the SIMCA software and MetaboAnalyst website. The results revealed that 50 active compounds and 45 key targets were screened and clustered with 20 approved drugs. The NF-κB signaling pathway, oxidative stress, and glutamine metabolism were associated with the therapeutic mechanism of SXD in acute bronchitis. In vivo experiments showed that SXD may maintain the production of inflammatory factors by regulating the PI3K/Akt/NF-κB signaling pathway, improving the metabolism of glutamine and glutamate to reduce oxidative stress, and inhibiting apoptosis. Simultaneously, the possibility of using SXD as an adjuvant drug for COVID-19 treatment was also revealed. This research will lay the foundation for the modern clinical application of SXD and promote the promotion and innovation of TCM.


Subject(s)
Bronchitis , COVID-19 , Drugs, Chinese Herbal , Animals , Bronchitis/drug therapy , COVID-19/drug therapy , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Glutamine , Humans , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases , Rats , Smoke
14.
Environ Sci Pollut Res Int ; 29(49): 74208-74224, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1872662

ABSTRACT

Lianhuaqingwen (LH), one traditional Chinese medicine (TCM), has been used to treat the coronavirus disease 2019 (COVID-19), but its ecotoxicity with potential human health security has not been well investigated. To overcome such adverse effects and improve its medication efficacy, an intelligent multi-method integrated dietary scheme, screening, and performance evaluation approach was developed. Thirteen LH compounds were selected, and the main protease (Mpro) was used as the potential drug target. Resulted information showed that the more compounds of LH added, the higher medication efficacy obtained using multi-method integrated screening system, expert consultation method, and molecular dynamics simulation. Pharmacodynamic mechanism analysis showed that low total energy and polar surface area of LH active compound (i.e., ß-sitosterol) will contribute to the best therapeutic effect on COVID-19 using quantitative structure-activity relationships (QSAR) and sensitivity models. Additionally, when mild COVID-19 patients take LH with the optimum dietary scheme (i.e., ß-lactoglobulin, α-lactalbumin, vitamin A, vitamin B, vitamin C, carotene, and vitamin E), the medication efficacy were significantly improved (23.58%). Pharmacokinetics and toxicokinetics results showed that LH had certain human health risks and ecotoxicity. This study revealed the multi-compound interaction mechanism of LH treatment on COVID-19, and provided theoretical guidance for improving therapeutic effect, evaluating TCM safety, and preventing human health risk.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Ascorbic Acid , Drugs, Chinese Herbal/pharmacology , Environmental Health , Humans , Lactalbumin , Lactoglobulins , Medicine, Chinese Traditional , Peptide Hydrolases , SARS-CoV-2 , Vitamin A , Vitamin E , Vitamins
15.
J Med Microbiol ; 71(5)2022 May.
Article in English | MEDLINE | ID: covidwho-1853315

ABSTRACT

Introduction. As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for discovering anti-COVID-19 drugs.Hypothesis/Gap Statement. We proposed that Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) may have potential value in the treatment of COVID-19 patients by regulating immune response, protecting the cardiovascular system, inhibiting the production of inflammatory factors, and blocking virus invasion and replication processes.Aim. We aimed to explore the feasibility and molecular mechanisms of RS against COVID-19, to provide a reference for basic research and clinical applications.Methodology. Through literature mining, it is found that a Chinese herbal pair, RS, has potential anti-COVID-19 activity. In this study, we analysed the feasibility of RS against COVID-19 by high-throughput molecular docking and molecular dynamics simulations. Furthermore, we predicted the molecular mechanisms of RS against COVID-19 based on network pharmacology.Results. We proved the feasibility of RS anti-COVID-19 by literature mining, virtual docking and molecular dynamics simulations, and found that angiotensin converting enzyme 2 (ACE2) and 3C-like protease (3 CL pro) were also two critical targets for RS against COVID-19. In addition, we predicted the molecular mechanisms of RS in the treatment of COVID-19, and identified 29 main ingredients, 21 potential targets and 16 signalling pathways. Rhein, eupatin, (-)-catechin, aloe-emodin may be important active ingredients in RS. ALB, ESR1, EGFR, HMOX1, CTSL, and RHOA may be important targets against COVID-19. Platelet activation, renin secretion, ras signalling pathway, chemokine signalling pathway, and human cytomegalovirus infection may be important signalling pathways against COVID-19.Conclusion. RS plays a key role in the treatment of COVID-19, which may be closely related to immune regulation, cardiovascular protection, anti-inflammation, virus invasion and replication processes.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , COVID-19 Vaccines , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Feasibility Studies , Flavonoids , Humans , Molecular Docking Simulation , Rhizome , SARS-CoV-2
16.
Eur Rev Med Pharmacol Sci ; 26(8): 2651-2661, 2022 04.
Article in English | MEDLINE | ID: covidwho-1836394

ABSTRACT

OBJECTIVE: The study aims to predict the target and molecular mechanism of Xuebijing injection in the treatment of novel coronavirus-induced acute respiratory distress syndrome (ARDS), based on network pharmacology. MATERIALS AND METHODS: Chinese and English studies were searched to obtain the main active components of Xuebijing injection. ETCM, TCMSP and Targetnet online databases were adopted used to predict Xuebijing therapeutic targets. GeneCards, CTD and OMIM databases were researched used to research for the novel coronavirus Disease-2019 (COVID-19) and ARDS-related targets. Integrate analysis was carried out to obtain the targets of Xuebijing injection in the treatment of ARDS caused by novel coronavirus. STRING was adopted to analyze the interaction of common target proteins. GO and KEGG enrichment analyses were carried out using Bioconductor bioinformatics software package based on R software. Network visualization was performed with Cytoscape software. RESULTS: A total of 30 main active components in Xuebijing injection were collected in this study, which can act on 615 targets. The core components of Xuebijing injection in treating the coronavirus-induced ARDS are Ferulic acid, Ethyl ferulate, Albiflorin, Caffeic acid, Rosmarinic acid, Naringenin, Quercetin. Xuebijing injection has 56 target points for the treatment of ARDS caused by the novel coronavirus, among which AKT1, TNF, CASP3 and STAT3 are the core ones. The main molecular mechanisms of Xuebijing injection in treating the coronavirus-induced ARDs include PI3K-Akt, TNF, STAT3, NF-κB and apoptosis-related pathways. CONCLUSIONS: Xuebijing mainly treats ARDS caused by the novel coronavirus through anti-inflammation, anti-apoptosis, and regulation of immunity since it has the characteristics of multi-component, multi-target and multi-pathway.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Respiratory Distress Syndrome , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Humans , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2
17.
BMC Complement Med Ther ; 22(1): 56, 2022 Mar 03.
Article in English | MEDLINE | ID: covidwho-1833306

ABSTRACT

BACKGROUND: Novel Corona Virus Disease 2019 (COVID-19) is closely associated with cytokines storms. The Chinese medicinal herb Artemisia annua L. (A. annua) has been traditionally used to control many inflammatory diseases, such as malaria and rheumatoid arthritis. We performed network analysis and employed molecular docking and network analysis to elucidate active components or targets and the underlying mechanisms of A. annua for the treatment of COVID-19. METHODS: Active components of A. annua were identified through the TCMSP database according to their oral bioavailability (OB) and drug-likeness (DL). Moreover, target genes associated with COVID-19 were mined from GeneCards, OMIM, and TTD. A compound-target (C-T) network was constructed to predict the relationship of active components with the targets. A Compound-disease-target (C-D-T) network has been built to reveal the direct therapeutic target for COVID-19. Molecular docking, molecular dynamics simulation studies (MD), and MM-GBSA binding free energy calculations were used to the closest molecules and targets between A. annua and COVID-19. RESULTS: In our network, GO, and KEGG analysis indicated that A. annua acted in response to COVID-19 by regulating inflammatory response, proliferation, differentiation, and apoptosis. The molecular docking results manifested excellent results to verify the binding capacity between the hub components and hub targets in COVID-19. MD and MM-GBSA data showed quercetin to be the more effective candidate against the virus by target MAPK1, and kaempferol to be the other more effective candidate against the virus by target TP53. We identified A. annua's potentially active compounds and targets associated with them that act against COVID-19. CONCLUSIONS: These findings suggest that A. annua may prevent and inhibit the inflammatory processes related to COVID-19.


Subject(s)
Artemisia annua , COVID-19 , Drugs, Chinese Herbal , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Humans , Molecular Docking Simulation , SARS-CoV-2
18.
J Healthc Eng ; 2022: 9248674, 2022.
Article in English | MEDLINE | ID: covidwho-1822117

ABSTRACT

The first reported case of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei, China. Thereafter, it spread through China and worldwide in only a few months, reaching a pandemic level. It can cause severe respiratory illnesses such as pneumonia and lung failure. Since the onset of the disease, the rapid response and intervention of traditional Chinese medicine (TCM) have played a significant role in the effective control of the epidemic. Yinqiaosan (YQS) was used to treat COVID-19 pneumonia, with good curative effects. However, a systematic overview of its active compounds and the therapeutic mechanisms underlying its action has yet to be performed. The purpose of the current study is to explore the compounds and mechanism of YQS in treating COVID-19 pneumonia using system pharmacology. A system pharmacology method involving drug-likeness assessment, oral bioavailability forecasting, virtual docking, and network analysis was applied to estimate the active compounds, hub targets, and key pathways of YQS in the treatment of COVID-19 pneumonia. With this method, 117 active compounds were successfully identified in YQS, and 77 potential targets were obtained from the targets of 95 compounds and COVID-19 pneumonia. The results show that YQS may act in treating COVID-19 pneumonia and its complications (atherosclerosis and nephropathy) through Kaposi sarcoma-related herpesvirus infection and the AGE-RAGE signaling pathway in diabetic complications and pathways in cancer. We distinguished the hub molecular targets within pathways such as TNF, GAPDH, MAPK3, MAPK1, EGFR, CASP3, MAPK8, mTOR, IL-2, and MAPK14. Five of the more highly active compounds (acacetin, kaempferol, luteolin, naringenin, and quercetin) have anti-inflammatory and antioxidative properties. In summary, by introducing a systematic network pharmacology method, our research perfectly forecasts the active compounds, potential targets, and key pathways of YQS applied to COVID-19 and helps to comprehensively clarify its mechanism of action.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Anti-Inflammatory Agents , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional
19.
Comput Biol Med ; 146: 105549, 2022 07.
Article in English | MEDLINE | ID: covidwho-1803807

ABSTRACT

OBJECTIVE: Based on bioinformatics and network pharmacology, the treatment of Saussurea involucrata (SAIN) on novel coronavirus (COVID-19) was evaluated by the GEO clinical sample gene difference analysis, compound-target molecular docking, and molecular dynamics simulation. role in the discovery of new targets for the prevention or treatment of COVID-19, to better serve the discovery and clinical application of new drugs. MATERIALS AND METHODS: Taking the Traditional Chinese Medicine System Pharmacology Database (TCMSP) as the starting point for the preliminary selection of compounds and targets, we used tools such as Cytoscape 3.8.0, TBtools 1.098, AutoDock vina, R 4.0.2, PyMol, and GROMACS to analyze the compounds of SAIN and targets were initially screened. To further screen the active ingredients and targets, we carried out genetic difference analysis (n = 72) through clinical samples of COVID-19 derived from GEO and carried out biological process (BP) analysis on these screened targets (P ≤ 0.05)., gene = 9), KEGG pathway analysis (FDR≤0.05, gene = 9), protein interaction network (PPI) analysis (gene = 9), and compounds-target-pathway network analysis (gene = 9), to obtain the target Point-regulated biological processes, disease pathways, and compounds-target-pathway relationships. Through the precise molecular docking between the compounds and the targets, we further screened SAIN's active ingredients (Affinity ≤ -7.2 kcal/mol) targets and visualized the data. After that, we performed molecular dynamics simulations and consulted a large number of related Validation of the results in the literature. RESULTS: Through the screening, analysis, and verification of the data, it was finally confirmed that there are five main active ingredients in SAIN, which are Quercitrin, Rutin, Caffeic acid, Jaceosidin, and Beta-sitosterol, and mainly act on five targets. These targets mainly regulate Tuberculosis, TNF signaling pathway, Alzheimer's disease, Pertussis, Toll-like receptor signaling pathway, Influenza A, Non-alcoholic fatty liver disease (NAFLD), Neuroactive ligand-receptor interaction, Complement and coagulation cascades, Fructose and mannose metabolism, and Metabolic pathways, play a role in preventing or treating COVID-19. Molecular dynamics simulation results show that the four active ingredients of SAIN, Quercitrin, Rutin, Caffeic acid, and Jaceosidin, act on the four target proteins of COVID-19, AKR1B1, C5AR1, GSK3B, and IL1B to form complexes that can be very stable in the human environment. Tertiary structure exists. CONCLUSION: Our study successfully explained the effective mechanism of SAIN in improving COVID-19, and at the same time predicted the potential targets of SAIN in the treatment of COVID-19, AKR1B1, IL1B, and GSK3B. It provides a new basis and provides great support for subsequent research on COVID-19.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Saussurea , Aldehyde Reductase , COVID-19/drug therapy , Computational Biology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Molecular Targeted Therapy , Network Pharmacology , Rutin
20.
J Med Food ; 25(4): 355-366, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1795397

ABSTRACT

We investigated the molecular mechanism by which Houttuynia cordata Thunb (HCT) may intervene in coronavirus disease 2019 (COVID-19) and COVID-19-induced cytokine storms using network pharmacology and molecular docking approaches. Using the Traditional Chinese medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a "component-target-pathway" topology map of HCT for COVID-19 treatment was constructed using Cytoscape. Core target genes were analyzed using the STRING database, and the signal pathway map and biological mechanism of COVID-19 therapy were obtained using cluster profilers. Active components of HCT were docked with severe respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) using AutoDockTools. Data visualization and statistical analysis were conducted using the R program. A molecular dynamic simulation was carried out with the Groningen Machine for Chemical Simulation program. HCT had six active anti-COVID-19 ingredients and 45 molecular targets. Their crucial target proteins for COVID-19 treatment were the RELA (nuclear factor kappa B [NF-κB] p65 subunit), interleukin 6, and mitogen-activated protein kinase 1. In functional enrichment analysis, the potential molecular targets of active components of HCT for COVID-19 treatment belonged to 18 signaling pathways (adjusted P = 2.12E-11). Gene ontology obtained by Kyoto Encyclopedia of Genes and Genome enrichment screening showed that the primary mechanism of COVID-19 treatment was upregulation of protein kinase C followed by downregulations of T cell differentiation and proliferation and NF-κB signaling. Molecular docking showed that the active components of HCT (quercetin and kaempferol) had similar binding affinities for SARS-CoV-2 3CLpro and SARS-CoV-2 RdRp, primary COVID-19 target proteins as did clinically used drugs. These results were confirmed with molecular dynamics simulation. In conclusion, multiple components of HCT, especially quercetin and kaempferol, have the potential to treat COVID-19 infection and COVID-19-induced cytokine storm by targeting multiple proteins.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Houttuynia , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional/methods , Molecular Docking Simulation , NF-kappa B , Quercetin , RNA-Dependent RNA Polymerase , SARS-CoV-2
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