Perspective Of Pharmacology Research Articles

Exploring the Mechanism of Hawthorn Leaves Against Coronary Heart Disease Using Network Pharmacology and Molecular Docking.

Hawthorn leaves, which is a traditional Chinese medicine (TCM), has been used for treating coronary heart disease (CHD) for a long time in China. But the limited understanding of the main active components and molecular mechanisms of this traditional medicine has restricted its application and further research. The active compounds of hawthorn leaves were obtained from TCMSP database and SymMap database. The targets of it were predicted based on TCMSP, PubChem, Swiss Target Prediction, and SymMap database. The putative targets of CHD were gathered from multi-sources databases including the Online Mendelian Inheritance in Man (OMIM) database, the DrugBank database, the GeneCards database and the DisGeNet database. Network topology analysis, GO and KEGG pathway enrichment analyses were performed to select the key targets and pathways. Molecular docking was performed to demonstrate the binding capacity of the key compounds to the predicted targets. Furthermore, RAW264.7 cells stimulated by lipopolysaccharides (LPS) were treated with three effective compounds of hawthorn leaves to assess reliability of prediction. Quercetin, isorhamnetin and kaempferol were main active compounds in hawthorn leaves. Forty four candidate therapeutic targets were identified to be involved in protection of hawthorn leaves against CHD. Additionally, the effective compounds of it had good binding affinities to PTGS2, EGFR, and MMP2. Enrichment analyses suggested that immune inflammation related biological processes and pathways were possibly the potential mechanism. Besides, we found that three predicted effective compounds of hawthorn leaves decreased protein expression of PTGS2, MMP2, MMP9, IL6, IL1B, TNFα and inhibited activation of macrophage. In summary, the present study demonstrates that quercetin, kaempferol and isorhamnetin are proved to be the main effective compounds of hawthorn leaves in treatment of CHD, possibly by suppressing expression of PTGS2, MMP2, MMP9, inflammatory cytokines and macrophages viability. This study provides a new understanding of the active components and mechanisms of hawthorn leaves treating CHD from the perspective of network pharmacology.

Mechanisms of Compound Sophora flavescens (Kushen) Decoction for the Treatment of Ulcerative Colitis based on Network Pharmacology and Molecular Docking Technology.

The compound Sophora flavescenes (Kushen) decoction was found to reduce the inflammatory symptom of Ulcerative Colitis (UC). However, there exists a very limited understanding of the molecular pharmacological mechanisms. This study aimed to explore the mechanism of compound Sophora flavescens (Kushen) decoction in treating ulcerative colitis from the perspective of network pharmacology. Active components and potential targets of compound Sophora flavescens (Kushen) decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. GeneCards and other databases were used to predict and screen ulcerative colitis-related genes. Cytoscape software was applied to construct the "drugactive component-disease-target" network. GO function and KEGG pathway enrichment analyses revealed the potential pathway of the compound Sophora flavescenes (Kushen) decoction for UC. After the screening, a total of 124 active ingredients and 163 potential therapeutic targets for UC were obtained from the compound Sophora flavescens (Kushen) decoction. Protein interaction network analysis showed that 15 key targets could be identified for the possible treatment of UC. GO and KEGG analyses showed that the active ingredients in the compound Sophora flavescens (Kushen) decoction were mainly enriched in 2556 biological processes and 172 signaling pathways. The study showed that the compound Sophora flavescens (Kushen) decoction has therapeutic effects on UC through multi-component, multi-target, and multi-pathway.

Potential metal-related strategies for prevention and treatment of COVID-19.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed severe threats to human health, public safety, and the global economy. Metal nutrient elements can directly or indirectly take part in human immune responses, and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years, providing potential solutions to the prevention and treatment of COVID-19. Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bioactivities, demonstrating irreplaceable advantages in pharmacology. This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology. The current and potential utilization of metal-based drugs is briefly introduced. Specifically, metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19.Graphic abstract

Insight in triazine chromatographic and microbiological analysis: A brief review

Triazine is the six-membered heterocyclic ring that contains three nitrogen?s instead of the carbon- hydrogen unit in the benzene. The triazine derivatives are very attractive from the perspective of agriculture, pharmacology and medicine for a long period of time. They possess a versatile pharmacophore which enables them to express diverse biological activities such as pesticidal, antibacterial, antifungal, antiendotoxin, antileishmanial, antitubercular and anticancer activity. This review represents a summarized report of the chromatographic and microbiological analysis of the triazine derivatives published in past five years.

Study on the Prognosis Effect of Traditional Chinese Medicine Treatment in DR Patients Based on the Perspective of Network Pharmacology.

Diabetes damages the eye in many ways, but the most common eye complication is retinopathy. Of the 246 million people with diabetes worldwide, about 30% will be at risk of developing diabetic retinopathy. In addition to impairing vision, the presence of diabetic retinopathy also means an increased risk of life-threatening systemic vascular complications. To prevent the occurrence and development of diabetic retinopathy, the research and development of new drugs for diabetic retinopathy is the primary task. Because of its characteristics of holistic view and dialectical view, traditional Chinese medicine has a good effect in the treatment of complex diseases. However, due to the characteristics of complex components, numerous targets, and synergistic effects that are important, and its compound prescriptions, the modernization of traditional Chinese medicine has been hindered. The rise of network pharmacology in recent years provides a good opportunity for the development of traditional Chinese medicine. Network pharmacology aims to explore the relationship between drugs and diseases from a holistic perspective, discover drug targets, and guide the development of new drugs. In terms of methodology, network pharmacology has the characteristics of integrity and systematicness, which just coincides with the principle of consultation in traditional Chinese medicine. In this paper, from the perspective of the application of traditional Chinese medicine, TCMSP software was used to retrieve the active ingredients in traditional Chinese medicine, and the corresponding targets of the active ingredients were obtained. We then performed GO annotation analysis and KEGG pathway analysis on the targets using DAVID software. We further used Cytoscape software to build an active ingredient-target-pathway network model. Through network pharmacology research, it has been shown that Fufang Xueshuantong may treat diabetic retinopathy through multiple pathways such as intravascular growth factor signaling pathway, mitogen-activated protein kinase signaling pathway, and Toll sample receptor signaling pathway, reflecting the multicomponent traditional Chinese medicine compound and multitarget and multichannel characteristics. The research in this paper provides a theoretical basis for the pharmacological mechanism of traditional Chinese medicine in the treatment of diabetic retinopathy.

Induction of PI3K/Akt-Mediated Apoptosis in Osteoclasts Is a Key Approach for Buxue Tongluo Pills to Treat Osteonecrosis of the Femoral Head.

The Buxue Tongluo pill (BTP) is a self-made pill with the functions of nourishing blood, promoting blood circulation, dredging collaterals, and relieving pain. It consists of Angelica sinensis (Oliv.) Diels, Pheretima aspergillum (E.Perrier), Panax notoginseng (Burk.) F. H. Chen, Astragalus membranaceus (Fisch.) Bge, and Glycyrrhiza uralensis Fisch. Various clinical practices have confirmed the therapeutic effect of BTP on osteonecrosis of the femoral head (ONFH), but little attention has been paid to the study of its bioactive ingredients and related mechanisms of action. In this study, UPLC/MS-MS combined with GEO data mining was used to construct a bioactive ingredient library of BTP and a differentially expressed gene (DEG) library for ONFH. Subsequently, Cytoscape (3.7.2) software was used to analyze the protein–protein interaction between BTP and DEGs of ONFH to screen the key targets, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 34 bioactive compounds were screened, which acted on 1,232 targets. A total of 178 DEGs were collected, and 17 key genes were obtained after two screenings. By bioinformatics annotation on these key genes, a total of 354 gene ontology (GO) functional annotation analyses and 42 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. The present study found that GO and KEGG enrichment were mainly related to apoptosis, suggesting that BTP may exert an anti-ONFH effect by promoting osteoclast apoptosis. Experiments in vitro demonstrated that BTP could increase the mitochondrial membrane potential (MMP) and induce remarkable apoptosis in osteoclasts. Furthermore, we determined the apoptosis marker of cleaved(C)-caspase-3, bcl-2, and bax and found that BTP could upregulate the C-caspase-3 and bax expression in osteoclasts and decrease the expression of bcl-2, p-Akt, and p-PI3K in a dose-dependent manner, indicating that BTP could induce PI3K/Akt-mediated apoptosis in osteoclasts to treat ONFH. This study explored the pharmacodynamic basis and mechanism of BTP against ONFH from the perspective of systemic pharmacology, laying a foundation for further elucidating the therapeutic effects of BTP against ONFH.

Analysis of the Composition and Anti-Rheumatoid Arthritis Mechanism of Qintengtongbi Decoction Based on Network Pharmacology

Qintengtongbi Decoction (QTTBD) is a traditional prescription for rheumatoid arthritis (RA) treatment in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, southern China's Guangxi Zhuang Autonomous Region. However, there is not yet any analysis on its active compounds or action mechanism for treating RA. Moreover, the prescription has not been investigated from the perspective of network pharmacology. Therefore, this study aimed to analyze the compounds QTTBD and their potential pharmacological effects and the mechanism by which they treat RA via an integrated network pharmacology approach. With the aid of the relevant database tools and research indices, 188 compounds and 272 related drug targets genes/proteins were collected from QTTBD through the compound-target network, and 175 common gene targets between the QTTBD and RA were obtained by Venn 2.1. Finally, the top 10 gene targets and pathways were identified through the protein–protein interaction network, gene ontology, and KEGG pathway analysis: the gene targets include AKT1, IL6, TP53, VEGFA, MAPK3, TNF, CASP3, JUN, EGF, and EGFR; the pathways include oxytocin signaling pathway, amphetamine addiction, graft-versus-host disease, ovarian steroidogenesis, cGMP-PKG signaling pathway, Rap1 signaling pathway, allograft rejection, cytokine–cytokine receptor interaction, regulation of lipolysis in adipocytes and inflammatory mediator regulation of transient receptor potential channels. Therefore, it is concluded that a network pharmacology-based approach can help reveal and clarify the anti-RA role of QTTBD, and provide a scientific basis for further research into the mechanism.

Deciphering the Therapeutic Mechanisms of Wuzi Ershen Decoction in Treating Oligoasthenozoospermia through the Network Pharmacology Approach.

Background Infertility affects approximately 15% of couples around the world, and male factors are accounted for 40–50%. Oligoasthenozoospermia is the most common reason for male infertility. Unfortunately, effective drug therapy is still lacking except for assisted reproductive technology (ART). Previous researchers found that Wuzi Ershen decoction (WZESD) can increase sperm count, enhance sperm vitality, and improve semen quality. However, the pharmacological mechanisms remain unclear. Methods In this study, we screened compounds and predicted the targets of WZESD based on the TCMSP and BATMAN-TCM database combined with literature searching in the PubMed database. We obtained proteins related to oligoasthenozoospermia through GeneCards and submitted them to STRING to obtain the protein-protein interaction (PPI) network. Potential targets of WZESD were mapped to the network, and the hub targets were screened by topology. We used online platform Metascape and Enrichr for GO and KEGG enrichment analyses. AutoDock Vina was utilized for further verification of the binding mode between compounds and targets. Results Totally, 276 bioactive compounds were obtained and targeted 681 proteins. 446 oligoasthenozoospermia disease-specific proteins were acquired, and further bioinformatics analysis found that they were mainly involved in the formation of gametes, meiosis, and sperm differentiation. Protein interaction network analysis revealed that target proteins of WZESD were associated with oligoasthenozoospermia disease-specific proteins. The 79 targets of disease-specific proteins, which were anchored by WZESD, mainly participate in the cellular response to the organic cyclic compound, regulation of the apoptotic process, nitricoxide biosynthetic and metabolic process, oxidative stress, and protein phosphorylation regulation, which are the causes for oligoasthenozoospermia. Molecular docking simulation further validated that bioactive compounds originated from WZESD with targeted proteins showed high binding efficiency. Conclusions This study uncovers the therapeutic mechanisms of WZESD for oligoasthenozoospermia treatment from the perspective of network pharmacology and may provide a valuable reference for further experimental research studies and clinical applications.

Uncovering the anti-NSCLC effects and mechanisms of gypenosides by metabolomics and network pharmacology analysis

Ethnopharmacological relevanceLung cancer is the chief reason of cancer death worldwide, and non-small cell lung cancer (NSCLC) make up the majority of lung cancers. Gypenosides are the main active constituents from Gynostemma pentaphyllum. Previous studies showed that they were used to remedy many cancers. The effect of gypenosides on NSCLC has never been studied from the perspective of network pharmacology and metabolomics. The mechanism is still not clear and remains to be explored. Aim of the studyTo explore the anti-NSCLC activity and mechanism of gypenosides in A549 cells. Material/methodsGypenosides of G. pentaphyllum were detected by HPLC-MS. The cytotoxicity was detected by MTT assay. The migration, cell cycle and apoptosis of gypenosides were studied by wound healing assay, JC-1 assay and flow cytometry. The mechanism of gypenosides on NSCLC was studied by metabolomics and network pharmacology. Some key proteins and pathways were further confirmed by Western blot. ResultsEleven gypenosides were detected by HPLC-MS. Gypenosides could suppress the proliferation of A549 cells, inhibit the migration of A549 cells, induce apoptosis and arrest cell cycle in G0/G1 phase. Metabolomics and network pharmacology approach revealed that gypenosides might affect 17 metabolite related proteins by acting on 9 candidate targets (STAT3, VEGFA, EGFR, MMP9, IL2, TYMS, FGF2, HPSE, LGALS3), thus resulting in the changes of two metabolites (uridine 5′-monophosphate, D-4′-Phosphopantothenate) and two metabolic pathways (pyrimidine metabolism; pantothenate and CoA biosynthesis). Western blotting indicated that gypenosides might inhibit A549 cells through MMP9, STAT3 and TYMS to indirectly affect the pathways of pyrimidine metabolism, pantothenate and CoA biosynthesis. ConclusionsThis study revealed that metabolomics combined with network pharmacology was conducive to understand the anti-NSCLC mechanism of gypenosides.

Molecular mechanism of reproductive toxicity induced by Tripterygium Wilfordii based on network pharmacology.

To explore the possible molecular mechanism of reproductive toxicity of Tripterygium wilfordii from the perspective of network pharmacology and bioinformatics.The compounds of T wilfordii were obtained by querying the relevant Chinese medicine database, the effective compounds were screened and the corresponding targets were obtained, and then compared with the reproductive toxicities related to disease targets obtained from the disease gene database to infer the potential toxic targets of reproductive toxicity of T wilfordii. Then, the key targets of reproductive toxicity of T wilfordii were screened using Search Tool for the Retrieval of Interacting Genes/Protein and Cytoscape. The gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as module analysis, were performed on the key targets using Database for Annotation, Visualization, and Integrated Discovery and Cytoscape, respectively. Finally, the network between effective compounds-toxic targets was conducted to see how the compounds interacted.A total of 48 effective compounds and 482 potential toxic targets related to the reproductive toxicity of T wilfordii were screened. The enrichment analysis results showed that the key targets were mainly enriched in biological processes such as response to drug, ionotropic glutamate receptor signaling pathway, and KEGG pathways such as neuroactive ligand-receptor interaction, cAMP signaling pathway. In the protein-protein interaction network of potential toxic targets, there were 78 key targets such as TP53, INS, IL6, AGT, ADCY3, and so on. Enrichment analysis of the top module with 19 genes from module analysis indicated that T wilfordii might cause reproductive toxicity by gene ontology terms and KEGG pathways such as regulation of vasoconstriction, G-protein coupled receptor signaling pathway, inflammatory response, cAMP signaling pathway, and so on. In the network between effective compounds of T wilfordii and key targets, there were 5 compounds with high degree including Tingenone, Wilfordic Acid, Abruslactone A, Nobilin, and Wilforlide B.The complex molecular mechanism of reproductive toxicity of T wilfordii can be preliminarily elucidated with the help of the network pharmacology method, and the analysis results can provide some reference for the further mechanism research of reproductive toxicity of T wilfordii.

Preliminary therapeutic and mechanistic evaluation of S-allylmercapto-N-acetylcysteine in the treatment of pulmonary emphysema

The objective of this work was to study the effects and mechanisms of S-allylmercapto-N-acetylcysteine (ASSNAC) in the treatment of pulmonary emphysema based on network pharmacology analysis and other techniques. Firstly, the potential targets associated with ASSNAC and COPD were integrated using public databases. Then, a protein–protein interaction network was constructed using String database and Cytoscape software. The Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on DAVID platform. The molecular docking of ASSNAC with some key disease targets was implemented on the SwissDock platform. To verify the results of the network pharmacology, a pulmonary emphysema mice model was established and treated with ASSNAC. Besides, the expressions of the predicted targets were detected by immunohistochemistry, Western blot analysis or enzyme-linked immunosorbent assay. Results showed that 33 overlapping targets are achieved, including CXCL8, ICAM1, MAP2K1, PTGS2, ACE and so on. The critical pathways of ASSNAC against COPD involved arachidonic acid metabolism, chemokine pathway, MAPK pathway, renin-angiotensin system, and others. Pharmacodynamic experiments demonstrated that ASSNAC decreased the pulmonary emphysema and inflammation in the pulmonary emphysema mice. Therefore, these results confirm the perspective of network pharmacology in the target verification, and indicate the treatment potential of ASSNAC against COPD.

Predictive analysis of quality markers of Coptidis Rhizoma based on network pharmacology and multivariate statistical analysis

Coptidis Rhizoma, as a bulk medicinal material, is in great demand in clinical practice. Its quality is uneven in the market due to the mixture of genuine, counterfeit and adulterants. Therefore, it is particularly important to establish a quality control system for Coptidis Rhizoma. Based on the concept of Chinese medicine quality marker(Q-marker), the potential quality markers of Coptidis Rhizoma were analyzed and predicted from the perspective of chemistry and pharmacology. The sources of the Q-markers of Coptidis Rhizoma were identified by literature retrieval. The potential Q-markers were then screened through the visualization of the "components-targets-pathways" network. High performance liquid chromatography(HPLC) was used to establish a multi-indicator qualitative and quantitative control method featuring fingerprints for 10 batches of Coptidis Rhizoma. A supervised mode of orthogonality partial least squares method-discriminant analysis(OPLS-DA) was used to screen the main marker components that caused differences between groups. The literature review results showed that the alkaloids were the main source of Coptidis Rhizoma Q-markers.The fingerprints of 13 common peaks were successfully established, and berberine, palmatine, berberine and epiberberine were selected as Q-markers of Coptidis Rhizoma, and their contents were determined.Based on the concept of the Q-marker of traditional Chinese medicine, the four components can be selected as the Q-marker of Coptidis Rhizoma after comprehensive consideration. The results of this study are not only conducive to the quality evaluation of Coptidis Rhizoma on the market, but also provide a reference for the overall quality control of Coptidis Rhizoma and lay foundation for the future exploration of the mechanism of Coptidis Rhizoma.

To explore the mechanism of action of Irpex lacteus treatment of hyperuricemia from the perspective of network pharmacology

Objective: To explore the active ingredients and mechanism of Irpex lacteus against HUA (hyperuricemia) by using network pharmacology and molecular docking technology. Methods: Through literature search and collection, drug-like screening, target prediction, construct a target library of chemical components related to Irpex lacteus; search and construct HUA disease target library through disease database. The PPI network of the crossover gene between the components of Irpex lacteus and HUA was constructed using STRING and Cytoscape; the GO function enrichment analysis of the crossover genes and the enrichment analysis of the KEGG signaling pathway were realized through the Metascape database; the purpose of the “target-signal pathway” network was to analyze its specific mechanism of action; molecular docking to verify the binding ability of the main active ingredients and key targets. Results: 56 active ingredients were screened, the core target of PPI network mitogen-activated protein kinase 3(MAPK3), mitogen-activated protein kinase ’(Mitogen-activated protein kinase 1, MAPK1), etc.; involved 1387 GO biological processes, 48 cell components, and 113 molecular functions; signaling pathway involved AGE-RAGE signaling pathway in diabetes complications, PI3K-Akt signaling pathway, IL-17 signaling pathway, etc; molecular docking results show that the core component tremutins A/C/E had good docking activity with each target. Conclusion: The related products of Irpex lacteus can treat HUA through multiple components, multiple targets, and multiple pathways, which could provide reference for further research and development.

GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide.

Oleoylethanolamide and palmitoylethanolamide are members of the fatty acid ethanolamide family, also known as acylethanolamides. Their physiological effects, including glucose homeostasis, anti-inflammation, anti-anaphylactic, analgesia, and hypophagia, have been reported. They have affinity for different receptor proteins, including nuclear receptors such as PPARα, channels such as TRPV1, and membrane receptors such as GPR119 and GPR55. In the present review, the pathophysiological functions of fatty acid ethanolamides have been discussed from the perspective of receptor pharmacology and drug discovery.

Mechanism of Wumei Pill in the Treatment of Non-Erosive reflux disease from the Perspective of Network Pharmacology and Molecular docking

Mechanism of Wumei Pill in the Treatment of Non-Erosive reflux disease from the Perspective of Network Pharmacology and Molecular docking

Effect of regulating qi and invigorate blood circulation method on hemorrheology in rats with acute blood stasis syndrome and its network pharmacology research

To observe the effect of regulating qi and invigorate blood circulation method on hemorrheology in rats with acute blood stasis syndrome from the perspective of modern pharmacology, and use network pharmacology to explain its mechanism. Forty male Wistar rats were randomly divided into 6 groups. Except the blank control group, the other groups were injected with adrenaline hydrochloride and ice bath to establish the acute blood stasis syndrome model. Each group were administered Xuefu Zhuyu D ecoction, Jinlingzi Powder, Taohong Siwu Decoction, and Yanhusuo Decoction, and t he blank control group and model control group were given the same volume of saline, respectively. The blood rheology indexes such as red blood cell aggregation index of rats were measured. The TCMSP and Batman database were used to search for chemical components and targets of Jinlingzi Powder, and protein interaction analysis, GO enrichment analysis and KEGG analysis were performed on the common targets. The experimental results show that, compared with the model group, the blood rheology index levels of the Yanhusuo group and Taohong Siwu Decoction group are reduced, while the blood rheology index levels of the Xuefu Zhuyu Decoction group and the Jinlingzi S an group are significantly reduced. The network pharmacology predicts that Jinlingzi Powder has 44 active ingredients and 34 drug-disease shared targets, and KEGG analyzes 61 signaling pathways. Conclusion: IN the case of blood stasis syndrome, the effect of regulating qi with invigorate blood circulation is better than that of regulating qi alone. Network pharmacologic prediction showed that TNF signaling pathway was strongly correlated with hemorheology, and its action pathway was closely related to key tar gets IL6, TNF, CASP3.

Emulgel: An opportunity in topical drug delivery development

An extraordinary part of dermatological pharmacology is the immediate openness of the skin as an objective organ for analysis and treatment. The blend of hydrophilic cells in hydrophobic intercellular material gives a hindrance to both hydrophilic and hydrophobic substances. Inside the significant gathering of semisolid arrangements, the utilization of straightforward gels has extended both in beautifiers and in drug arrangements. Despite numerous benefits of gels a significant impediment is in the conveyance of hydrophobic drugs. Many benefits of gels a significant limit is in the conveyance of hydrophobic medications. An extraordinary perspective of dermatological pharmacology is the immediate openness of the skin as an objective organ for analysis and treatment. The mix of hydrophilic cells in hydrophobic intercellular material gives a barrier to both hydrophilic and hydrophobic substances. Truth be told, the presence of a gelling specialist in the water stage changes over a classical emulsion into an emulgel. These emulgel are enjoying significant benefits on novel vesicular frameworks just as on conventional frameworks in different aspects. Various pervasion enhancers can potentiate the impact, So emulgels can be utilized as better skin drug conveyance frameworks over present systems. The utilization of emulgels can be expanded in analgesics and antifungal medications.

Systematic Pharmacology and GEO Database Mining Revealed the Therapeutic Mechanism of Xuefu Zhuyu Decoration for Atherosclerosis Cardiovascular Disease.

Background: Xuefu Zhuyu decoration (XFZYD), as a traditional Chinese compound recipe, has been used to treat atherosclerosis cardiovascular disease (ASCVD) for thousands of years in China, but its effective compounds and underlying treatment molecular mechanism remains promiscuous, which severely limits its clinical application.Methods: The effective components and their targets of XFZYD were predicted and screened based on the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The candidate therapeutic targets of ASCVD were screened by Pharmacogenomics Knowledgebase (PharmGKB) and Comparative Toxicogenomics Database (CTD). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Differentially expressed genes were identified using the GEO2R online tool. Molecular docking was performed by Schrodinger software. To assess the efficacy of the prediction, human umbilical vein endothelial cells (HUVECs) treated with the effective compound of XFZYD were used as the in vitro model.Results: A total of 108 effective compounds (including quercetin) and 137 candidate therapeutic targets were identified. Analyzing the relationships among effective compounds, candidate therapeutic targets, and signaling pathways, the therapy mechanisms of XFZYD were mainly reflected in the protection of vascular endothelium, anti-inflammatory, antioxidant stress, etc. Accordingly, we found the effective compound of XFZYD (quercetin) decreased intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressions and pro-inflammatory cytokines in HUVECs treated with lipopolysaccharide (LPS), and reduced the adhesion function of HUVECs with monocytes. The inhibitor of the predicted target protein (PTGS2) could further reduce the expressions of VCAM-1, ICAM-1, and TNF-α induced by LPS, and inhibit the adhesion function of HUVECs with monocytes, while PTGS2 agonists partially counteracted the protective effect of quercetin.Conclusions: In this study, the effective components and potential therapeutic targets of XFZYD for ASCVD treatment were explored from the perspective of systemic pharmacology. The effective component quercetin was verified to protect endothelial cells by reducing endothelial inflammatory response and impeding the attachment of monocytes against the predicted therapeutic target PTGS2.

Mechanism of Hindu Datura in the Treatment of Rheumatoid Arthritis from the Perspective of Network Pharmacology

Mechanism of Hindu Datura in the Treatment of Rheumatoid Arthritis from the Perspective of Network Pharmacology

Drug repurposing for COVID-19: could vitamin C combined with glycyrrhizic acid be at play by the findings of Li etal.'s database-based network pharmacology analysis?

The outbreak and pandemic of SARS-CoV-2 in 2019 has caused a severe public health burden and will challenge global health for the future. The discovery and mechanistic investigation of drugs against Coronavirus disease 2019 (COVID-19) is in deadly demand. The paper published by Li and colleagues proposed the hypothesis that vitamin C combined with glycyrrhizic acid in treating COVID-19 and its mechanistic investigation was performed by a database-based network pharmacology. In this letter, we present critical comments on the limitations and insufficiencies involved, from both the perspective of network pharmacology and current evidence on COVID-19.