scholarly journals Experimental evidence and network pharmacology-based analysis reveal the molecular mechanism of Tongxinluo capsule administered in coronary heart diseases

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Guode Li ◽  
Qingbo Xu ◽  
Kedong Han ◽  
Wenhe Yan ◽  
Chaopei Huang

Abstract Background: Tongxinluo (TXL) capsule, a polypharmacy derived from traditional Chinese medicine (TCM), has been widely used in coronary heart disease (CHD), while the underlying mechanism of TXL capsule is still unclear. The present study aimed at investigating the underlying mechanism of TXL acting on CHD patients and providing substantial evidence in molecular evidence by means of a network pharmacological analysis. Method: Active compounds and targeted genes of TXL were retrieved from TCM systems pharmacology (TCMSP) and TCM integrative database (TCMID). CHD and coronary artery disease were treated as search queries in GeneCards and Online Mendelian Inheritance in Man (OMIM) databases to obtain disease-related genes. Visualization of disease–targets network was performed under administration of Cytoscape software. Besides, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were administered. H9c2 cells were used to validate the predicted results in cardiomyocytes/reoxygenation model, and anti-inflammatory ability was examined. Results: A network of a total of 212 nodes and 1016 edges was obtained. Peptide and ubiquitin-like protein ligase binding occupied a leading position of GO enrichment. For KEGG analysis, fluid shear stress and atherosclerosis, as well as inflammation-related pathways were enriched. Cellular validation revealed the anti-inflammatory effect of β-sitosterol, eriodictyol, odoricarpin, and tirucallol as active compounds of TXL. Conclusion: Our study provided substantial molecular evidence that TXL capsule possessed the characteristics of multitargets with safe profile, and the main component is capable of regulating cytokine level in CHD patients.

Plants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1166
Author(s):  
Man Chu ◽  
Miranda Sin-Man Tsang ◽  
Ru He ◽  
Christopher Wai-Kei Lam ◽  
Zhi Bo Quan ◽  
...  

To examine the molecular targets and therapeutic mechanism of a clinically proven Chinese medicinal pentaherbs formula (PHF) in atopic dermatitis (AD), we analyzed the active compounds and core targets, performed network and molecular docking analysis, and investigated interacting pathways. Information on compounds in PHF was obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and target prediction was performed using the Drugbank database. AD-related genes were gathered using the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Network analysis was performed by Cytoscape software and protein-protein interaction was analyzed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources were applied for the enrichment analysis of the potential biological process and pathways associated with the intersection targets between PHF and AD. Autodock software was used to perform protein compound docking analysis. We identified 43 active compounds in PHF associated with 117 targets, and 57 active compounds associated with 107 targets that form the main pathways linked to oral and topical treatment of AD, respectively. Among them, quercetin, luteolin, and kaempferol are key chemicals targeting the core genes involved in the oral use of PHF against AD, while apigenin, ursolic acid, and rosmarinic acid could be used in topical treatment of PHF against AD. The compound–target–disease network constructed in the current study reveals close interactions between multiple components and multiple targets. Enrichment analysis further supports the biological processes and signaling pathways identified, indicating the involvement of IL-17 and tumor necrosis factor signaling pathways in the action of PHF on AD. Our data demonstrated the main compounds and potential pharmacological mechanisms of oral and topical application of PHF in AD.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Meng Jiang ◽  
Xing Su ◽  
Jianling Liu ◽  
Chunli Zheng ◽  
Xiaogang Li

Ethnopharmacological Relevance. Dragon’s blood (DB) is a widely used traditional Chinese medicine that has many pharmacological effects, including antiplatelet aggregation, promoting epidermal growth, and anti-inflammatory and antioxidant activities. The main component of Longxuetongluo capsule and Dragon’s blood dropping pills is DB’s standard phenolic extract, which was used for ischemic stroke prognosis in China. Aim of Study. To dissect the molecular mechanisms of Dragon’s blood (DB) in improving ischemic stroke prognosis. Materials and Methods. (1) Based on system-pharmacology platform, the potential active compounds of DB are screened out according to ADME. (2) The ischemic stroke-related targets are predicted by utilizing these active compounds as probes, mapping the targets to the CTD database to establish a molecular-target-disease network. (3) To analyze the mechanism of DB treatment for the prognosis of ischemic stroke, we used the Metascape and DAVID databases to construct “ischemic stroke pathways”. (4) PC12 cells were used to explore the protective effect of loureirin B on oxygen-glucose deprivation/reperfusion (OGD/R) injury, and BV-2 cells were used to determine the anti-inflammation effect of 4′,7-dihydroxyflavone. Results. Finally, we obtained 38 active compounds and 58 stroke-related targets. Network and pathway analysis indicate that DB is effective in the treatment of ischemic stroke by enhancing cell survival and inhibiting inflammatory and antiplatelet activation. In in vitro experiments, the main component loureirin B promoted the expression of HO-1 and Bcl-2 via positive regulation of PI3K/AKT/CREB and Nrf2 signaling pathways in PC12 cells against OGD/R damage. And the anti-inflammatory activity of 4′,7-dihydroxyflavone was related to the inhibition of COX-2, TNF-α, and IL-6 in LPS-induced BV-2 cells. Conclusions. In our study, the results illustrated that DB in improving ischemic stroke prognosis may involve enhancing cell survival and antioxidant, anti-inflammation, and antiplatelet activities.


2020 ◽  
Author(s):  
Lianzhou Huang ◽  
Zexiu Huang ◽  
Yuanqiu Chen ◽  
Xin Jin ◽  
Ji Xiao ◽  
...  

Abstract BackgroundHesperetin, an active ingredient derived from Citrus × aurantium L., possesses a wide range of biological activities, including anti-inflammatory, anti-oxidation, and anti-cancer activity. Notably, hesperetin has been proposed as a candidate for atherosclerosis owing to the lipid-regulating and anti-inflammatory effect, while the underlying mechanisms remains obscure.ResultsIn our present study, the pharmacological and molecular properties of hesperetin were first evaluated to determine the druggability of hesperetin. Subsequently, 53 hesperetin-atherosclerosis crossover targets were collected to establish the protein-protein interaction network. The result of Gene Ontology enrichment analysis indicated that the crossover targets were involved in the regulation of lipid metabolism and inflammatory response. Moreover, the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that the crossover targets were highly correlated with the pathogenesis of atherosclerosis, such as fluid shear stress and atherosclerosis pathway and the TNF signaling pathway. Finally, an entire hesperetin-target-pathway network was constructed to provide a systematic overview of the pharmacological mechanisms of action of hesperetin against atherosclerosis.ConclusionsThe pharmacological mechanisms of actions of hesperetin against atherosclerosis was unveiled based on biodata mining from the public database and the bioinformatics data analysis-based strategy in this study, contributing to a deeper understanding of the molecular mechanisms of hesperetin in the treatment of atherosclerosis. Based on the results of network pharmacology analysis, we can conclude that hesperetin is surely an excellent candidate for atherosclerosis. We believe our work would be beneficial for further research and development of hesperetin as a natural active ingredient derived from Citrus × aurantium L. for the treatment of atherosclerosis.


2020 ◽  
Author(s):  
Lvkeng Luo ◽  
Shuling Wu ◽  
Ruiqi Chen ◽  
Hongyu Rao ◽  
Wei Peng ◽  
...  

Abstract Background: Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen, Radix Paeoniae Rubra Curcumae Radix Gastrodiae Rhizoma and Radix Rhapontici. It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects. Methods:To more generally elucidate the underlying mechanisms in this study, we identified active ingredients in NSTC by a network pharmacology approach based on transcriptomics analysis and pharmacological experiments. Modified neurological severity scores and morphometric analysis using Nissl staining were employed to evaluate the neuroprotective effects of NSTC on ischemia stroke in mice. Results: The results showed that NSTC had preventive and protective effects on ischemia stroke, featuring repair of brain tissue during the sub-acute stage of stroke. This may attribute to the underlying mechanisms including anti-inflammatory, antioxidant, and anti-apoptotic activities, as well as an attenuation of excitatory amino acids (EAAs) toxicity of the active ingredients, especially the most active apigenin, from NSTC. Specifically, naringenin, calycosin, gastrodin, caffeic acid, paeoniflorin, and β -elemene seem to be also pharmacological active substances responsible for the anti-inflammatory effects. Meanwhile, 13-hydroxygemone, gastrodin, and p-hydroxybenzyl alcohol contributed to the attenuation of EAAs toxicity Furthermore, apigenin, naringenin, calycosin, gastrodin, and β-elemene accelerated the repair of brain ischemic tissue by up-regulating the expression of TGF-β1 levels.Conclusions: The present study identifies the active ingredients of NSTC and illustrates the underlying mechanism using a combination of network pharmacology, transcriptomics analysis, and pharmacological experiments.


2021 ◽  
Vol 16 ◽  
Author(s):  
Xiaolei Ma ◽  
Yinan Lu ◽  
Yang Lu ◽  
Zhili Pei

Background: Tufuling Qiwei Tangsan (TQTS) is a commonly used Mongolian medicine preparation against psoriasis in China. However, its mechanism of action and molecular targets for the treatment of psoriasis is still unclear. Network pharmacology can reveal the synergistic mechanism of drugs at the molecular, target and pathway levels, and is suitable for the complex study of traditional Chinese medicine formulations. However, it is rarely involved in the application of Mongolian medicine with the same holistic concept of traditional Chinese medicine. Method: In this paper, the active compounds of TQTS were collected and their targets were identified. Psoriasis-related targets were obtained by analyzing the differential expressed genes between psoriasis patients and healthy individuals. Then, the network concerning the interactions of potential targets of TQTS with well-known psoriasis-related targets was built. The core targets were selected according to topological parameters. And the enrichment analysis was carried out to explore the mechanism of action of TQTS. Moreover, molecular docking was performed to study the interaction between the selected ligands and receptors related to psoriasis. Result and Conclusion: Eighty-five active compounds of TQTS were screened, with corresponding 270 targets, and 313 differentially expressed genes were identified. Additionally, enrichment analysis showed that the targets of TQTS for treating psoriasis were mainly concentrated in multiple biological processes, including apoptosis, growth factor response,etc., and related pathways including PI3K-Akt and MAPK signaling pathway, and so on. Genes such as NFKB1, TP53 and MAPK1 are the key genes in the gene pathway network of TQTS against psoriasis. The 4 main active components of TQTS have certain binding activity with 13 potential targets, and the stability of interaction with AKT1 is the best, which indicate the potential mechanism of TQTS on psoriasis.


2020 ◽  
Author(s):  
Lvkeng Luo ◽  
Shuling Wu ◽  
Ruiqi Chen ◽  
Hongyu Rao ◽  
Wei Peng ◽  
...  

Abstract Background: Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen, Radix Paeoniae Rubra, Curcumae Radix, Gastrodiae Rhizoma and Radix Rhapontici. It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects.Methods:To more generally elucidate the underlying mechanisms in this study, we identified active ingredients in NSTC by a network pharmacology approach based on transcriptomics analysis and pharmacological experiments. Modified neurological severity scores and morphometric analysis using Nissl staining were employed to evaluate the neuroprotective effects of NSTC on ischemia stroke in mice.Results: The results showed that NSTC had preventive and protective effects on ischemia stroke, featuring repair of brain tissue during the sub-acute stage of stroke. This may attribute to the underlying mechanisms including anti-inflammatory, antioxidant, and anti-apoptotic activities, as well as an attenuation of excitatory amino acids (EAAs) toxicity of the active ingredients, especially the most active apigenin, from NSTC. Specifically, naringenin, calycosin, gastrodin, caffeic acid, paeoniflorin, and β -elemene seem to be also pharmacological active substances responsible for the anti-inflammatory effects. Meanwhile, 13-hydroxygemone, gastrodin, and p-hydroxybenzyl alcohol contributed to the attenuation of EAAs toxicity Furthermore, apigenin, naringenin, calycosin, gastrodin, and β-elemene accelerated the repair of brain ischemic tissue by up-regulating the expression of TGF-β1 levels.Conclusions: The present study identifies the active ingredients of NSTC and illustrates the underlying mechanism using a combination of network pharmacology, transcriptomics analysis, and pharmacological experiments.


2020 ◽  
Author(s):  
Lvkeng Luo ◽  
Shuling Wu ◽  
Ruiqi Chen ◽  
Hongyu Rao ◽  
Wei Peng ◽  
...  

Abstract Background Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen (TP), Radix Paeoniae Rubra (PR), Curcumae Radix (CR), Gastrodiae Rhizoma (GR) and Radix Rhapontici (RR). It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects. Methods To more generally elucidate the underlying mechanisms in this study, we identified active ingredients in NSTC by a network pharmacology approach based on transcriptomics analysis and pharmacological experiments. Modified neurological severity scores (mNSS) and morphometric analysis using Nissl staining were employed to evaluate the neuroprotective effects of NSTC on ischemia stroke in mice. Results The results showed that NSTC had preventive and protective effects on ischemia stroke, featuring repair of brain tissue during the sub-acute stage of stroke. This may attribute to the underlying mechanisms including anti-inflammatory, antioxidant, and anti-apoptotic activities, as well as an attenuation of excitatory amino acids (EAAs) toxicity of the active ingredients, especially the most active apigenin, from NSTC. Specifically, naringenin, calycosin, gastrodin, caffeic acid, paeoniflorin, and β -elemene seem to be also pharmacological active substances responsible for the anti-inflammatory effects. Meanwhile, 13-hydroxygemone, gastrodin, and p-hydroxybenzyl alcohol contributed to the attenuation of EAAs toxicity Furthermore, apigenin, naringenin, calycosin, gastrodin, and β-elemene accelerated the repair of brain ischemic tissue by up-regulating the expression of TGF-β1 levels. Conclusions The present study identifies the active ingredients of NSTC and illustrates the underlying mechanism using a combination of network pharmacology, transcriptomics analysis, and pharmacological experiments.


2021 ◽  
Vol 18 (10) ◽  
pp. 2125-2131
Author(s):  
Qing Zhang ◽  
Ruolan Li ◽  
Jia Liu ◽  
Wei Peng ◽  
Yongxiang Gao ◽  
...  

Purpose: To investigate by in silico screening the anti-inflammatory constituents of Cinnamomum cassia twigs. Methods: Information on the constituents of C. cassia twigs was retrieved from the online Traditional Chinese Medicines (TCM) database and literature. Inflammation-related target proteins were identified from DrugBank, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), Genetic Association Database (GAD), and PharmGKB. The identified compounds were filtered by Lipinski’s rules with Discovery Studio software. The “Libdock” module was used to perform molecular docking; LibdockScores and default cutoff values for hydrogen bonds and van der Waals interactions were recorded. LibdockScores between the prototype ligand and target protein were set as the threshold; compounds with higher LibdockScores than threshold were regarded as active compounds. Cytoscape software was used to construct active constituent-target protein interaction networks. Results: Sixty-nine potential inflammatory constituents with good drug-like properties in C. cassia twigs were screened in silico based on molecular docking and network pharmacology analysis. JAK2, mPEGS-1, COX-2, IL-1β, and PPARγ were considered the five most important target proteins. Compounds such as methyl dihydromelilotoside, hierochin B, dihydromelilotoside, dehydrodiconiferyl alcohol, balanophonin, phenethyl (E)-3-[4-methoxyphenyl]-2-propenoate, quercetin, and luteolin each interacted with more than six of the selected target proteins. Conclusion: C. cassia twigs possess active compounds with good drug-like properties that can potentially be developed to treat inflammation with multi-components on multi-targets.


2020 ◽  
Author(s):  
Can Wan ◽  
Ziyi Zhou ◽  
Yun Lu ◽  
Guangyao Zhang ◽  
Yefeng Cai ◽  
...  

Abstract Background: Previous studies have shown that Zhongfeng Xingnao Formula (ZXF) can effectively reduce the mortality of intracerebral hemorrhage (ICH), but the underlying mechanism of the treatment remained still unexplored. This study aimed to expound the potential mechanism of ZXF in the treatment of ICH through network pharmacology and molecular docking.Methods: The putative targets of ZXF were obtained from the TCMSP and Uniprot database, while the potential targets of ICH received from Drugbank, Genecards and OMIM database. Then through the Venn 2.1, the overlapping targets of disease and drug were gotten for the further study. The GO and KEGG enrichment analyses were performed by R version 4.0.2 software so that the signaling pathway was acquired to the subsequent analysis. Cytoscape was used to construct the drug-compound-target-pathway network and String was utilized for the protein-protein interaction network. What’s more, the interaction between compound and target was verified by the AutoDockTools and Autodock Vina. Results: There were a total of 166 ZXF-related targets and 1258 ICH-related targets obtained from the public databases. And 87 potential targets were both related to drug and disease. The GO enrichment analysis mainly involved receptor ligand activity, signaling receptor activator activity, and cytokine receptor binding, while the signaling pathway, such as Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, were significantly enriched in the KEGG enrichment analysis. The molecular docking elucidated that the aloe-emodin, beta-sitosterol, quercetin could bound well to the top five targets sorted by degree value.Conclusions: ZXF treated ICH through multiple compounds, multiple targets, and multiple pathways. The underlying mechanism of the treatment may be promoting angiogenesis, anti-inflammatory, anti-oxidative stress, and reversing atherosclerosis, which is of great significance for the treatment of ICH.


2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Pei Liu ◽  
Huachong Xu ◽  
Yucong Shi ◽  
Li Deng ◽  
Xiaoyin Chen

Background. The incidence of gout and hyperuricemia is increasing year by year in the world. Plantain is a traditional natural medicine commonly used in the treatment of gout and hyperuricemia, but the molecular mechanism of its active compounds is still unclear. Based on network pharmacology, this article predicts the targets and pathways of effective components of plantain for gout and hyperuricemia and provides effective reference for clinical medication. Method. Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SymMap databases were used to screen out the active compounds and their targets in plantain. GeneCards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM) databases were used to find the targets corresponding to gout and hyperuricemia. Venn diagram was used to obtain the intersection targets of plantain and diseases. The interaction network of the plantain active compounds-targets-pathways-diseases was constructed by using Cytoscape 3.7.2 software. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. Result. Seven active compounds were identified by network pharmacological analysis, including dinatin, baicalein, baicalin, sitosterol, 6-OH-luteolin, stigmasterol, and luteolin. Plantain plays a role in gout and hyperuricemia diseases by regulating various biological processes, cellular components, and molecular functions. The core targets of plantain for treating gout are MAPK1, RELA, TNF, NFKBIA, and IFNG, and the key pathways are pathways in cancer, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway, Chagas disease (American trypanosomiasis), and relaxin signaling pathway. The core targets of plantain for hyperuricemia are RELA, MAPK1, NFKBIA, CASP3, CASP8, and TNF, and the main pathways are pathways in cancer, apoptosis, hepatitis B, IL-17 signaling pathway, and toxoplasmosis. Conclusion. This study explored the related targets and mechanisms of plantain for the treatment of gout and hyperuricemia from the perspective of network pharmacological analysis, reflecting the characteristics of multiple components, multiple targets, and multiple pathways, and it provides a good theoretical basis for the clinical application of plantain.


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