Exploring the Mechanism of Action of Herbal Medicine (Gan-Mai-Da-Zao Decoction) for Poststroke Depression Based on Network Pharmacology and Molecular Docking

Background. Poststroke depression (PSD) is the most common and serious neuropsychiatric complication occurring after cerebrovascular accidents, seriously endangering human health while also imposing a heavy burden on society. Nevertheless, it is difficult to control disease progression. Gan-Mai-Da-Zao Decoction (GMDZD) is effective for PSD, but its mechanism of action in PSD is unknown. In this study, we explored the mechanism of action of GMDZD in PSD treatment using network pharmacology and molecular docking. Material and methods. We obtained the active components of all drugs and their targets from the public database TCMSP and published articles. Then, we collected PSD-related targets from the GeneCards and OMIM databases. Cytoscape 3.8.2 was applied to construct PPI and composite target disease networks. In parallel, the DAVID database was used to perform GO and KEGG enrichment analyses to determine the biological processes enriched in the treatment-related drugs in vivo. Finally, molecular docking was used to verify the association between the main active ingredients and their targets. Results. The network pharmacological analysis of GMDZD in PSD revealed 107 active ingredients with important biological effects, including quercetin, luteolin, kaempferol, naringenin, and isorhamnetin. In total, 203 potential targets for the treatment of this disease were screened, including STAT3, JUN, TNF, TPT53, AKT1, and EGFR. These drugs are widely enriched in a series of signaling pathways, such as TNF, HIF-1, and toll-like receptor. Moreover, molecular docking analysis showed that the core active components were tightly bound to their core targets, further confirming their anti-PSD effects. Conclusion. This prospective study was based on the integrated analysis of large data using network pharmacology technology to explore the feasibility of GMDZD for PSD treatment that was successfully validated by molecular docking. It reflects the multicomponent and multitarget characteristics of Chinese medicine and, more importantly, brings hope for the clinical treatment of PSD.

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Exploring The Mechanism of Action of Herbal Medicine (Gan-Mai-Da-Zao Decoction) For Post-Stroke Depression Based On Network Pharmacology And Molecular Docking

10.21203/rs.3.rs-508953/v1 ◽

2021 ◽

Author(s):

Zhi-Cong Ding ◽

Fang-Fang Xu ◽

Qi-Di Sun ◽

Bin Li ◽

Neng-Xing Liang ◽

...

Keyword(s):

Molecular Docking ◽

Drug Treatment ◽

Mechanism Of Action ◽

Network Pharmacology ◽

Active Ingredients ◽

Active Components ◽

Composite Target ◽

Post Stroke ◽

The Core ◽

Post Stroke Depression

Abstract Backgrounds: Post-stroke depression is the most common and serious neuropsychiatric complication occurring after cerebrovascular accidents, seriously endangering human health while also imposing a heavy burden on society. Even so, it is difficult to have drugs to contain the progression of the disease. It’s reported that Gan-Mai-Da-Zao decoction was effective to PSD, but it is unknown on its mechanism of action for PSD. In this study, we aimed to explore the possible mechanisms of action of Gan-Mai-Da-Zao decoction in the treatment of PSD using network pharmacology and molecular docking.Material and methods: We obtained the active components and their targets of all drugs from the public database TCMSP and published articles. Then, we collected the PSD-related targets from GeneCards and OMIM databases. Cytoscape 3.8.2 was applied to construct PPI and composite target disease networks. In parallel, the DAVID database was used to perform GO and KEGG enrichment analysis to obtain the biological processes involved in drug treatment diseases in vivo. Finally, molecular docking was used to verify the association between the main active ingredients and the targets.Results: The network pharmacological analysis of Gan-Mai-Da-Zao decoction for PSD identified 107 active ingredients with important biological effects, including quercetin, luteolin, kaempferol, naringenin, isorhamnetin, etc. A total of 203 potential targets for drug treatment of diseases were screened, including STAT3, JUN, TNF, TPT53, AKT1, EGFR, etc. They were found to be widely enriched in a series of signaling pathways such as TNF, HIF-1, and the Toll-Like receptor. Meanwhile, molecular docking analysis showed that the core active components were tightly bound to the core targets, further confirming their anti-PSD effects.Conclusion: This is a prospective study based on the integration and analysis of large data, using the technology of network pharmacology to explore the feasibility of Gan-Mai-Da-Zao decoction for the treatment of PSD, and successfully validated by molecular docking. It reflects the multi-component and multi-target characteristics of Chinese medicine, and more importantly, it also brings hope to the clinical treatment of PSD.

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Mechanism of Action of Bu-Fei-Yi-Shen Formula in Treating Chronic Obstructive Pulmonary Disease Based on Network Pharmacology Analysis and Molecular Docking Validation

BioMed Research International ◽

10.1155/2020/9105972 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Longchuan Wu ◽

Yu Chen ◽

Jiao Yi ◽

Yi Zhuang ◽

Lei Cui ◽

...

Keyword(s):

Molecular Docking ◽

Mechanism Of Action ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Chronic Obstructive ◽

Biological Functions ◽

Active Ingredients ◽

Obstructive Pulmonary Disease ◽

The Core ◽

Target Network

Objective. To explore the mechanism of action of Bu-Fei-Yi-Shen formula (BFYSF) in treating chronic obstructive pulmonary disease (COPD) based on network pharmacology analysis and molecular docking validation. Methods. First of all, the pharmacologically active ingredients and corresponding targets in BFYSF were mined by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the analysis platform, and literature review. Subsequently, the COPD-related targets (including the pathogenic targets and known therapeutic targets) were identified through the TTD, CTD, DisGeNet, and GeneCards databases. Thereafter, Cytoscape was employed to construct the candidate component-target network of BFYSF in the treatment of COPD. Moreover, the cytoHubba plug-in was utilized to calculate the topological parameters of nodes in the network; then, the core components and core targets of BFYSF in the treatment of COPD were extracted according to the degree value (greater than or equal to the median degree values for all nodes in the network) to construct the core network. Further, the Autodock vina software was adopted for molecular docking study on the core active ingredients and core targets, so as to verify the above-mentioned network pharmacology analysis results. Finally, the Omicshare database was applied in enrichment analysis of the biological functions of core targets and the involved signaling pathways. Results. In the core component-target network of BFYSF in treating COPD, there were 30 active ingredients and 37 core targets. Enrichment analysis suggested that these 37 core targets were mainly involved in the regulation of biological functions, such as response to biological and chemical stimuli, multiple cellular life processes, immunity, and metabolism. Besides, multiple pathways, including IL-17, Toll-like receptor (TLR), TNF, and HIF-1, played certain roles in the effect of BFYSF on treating COPD. Conclusion. BFYSF can treat COPD through the multicomponent, multitarget, and multipathway synergistic network, which provides basic data for intensively exploring the mechanism of action of BFYSF in treating COPD.

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Investigation of Active Ingredients and Mechanism of Sanao Decoction in the Treatment of Chronic Cough by Network Pharmacology

10.21203/rs.3.rs-127466/v1 ◽

2020 ◽

Author(s):

Mengke Sheng ◽

Xing Liu ◽

Qingsong Qu ◽

Xiaowen Wu ◽

Yuyao Liao ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Chronic Cough ◽

Fluid Shear Stress ◽

Oxidant Stress ◽

Network Pharmacology ◽

Ppi Network ◽

Active Ingredients ◽

Active Components ◽

Pathway Network

Abstract Background: Chronic cough significantly affects human health and quality of life. Studies have shown that Sanao Decoction（SAD）can clinically treat chronic cough. To investigate its mechanisms, we used the method of network pharmacology to conduct research at the molecular level.Methods: The active ingredients and their targets were screened by pharmacokinetics parameters from the traditional Chinese medicine system pharmacology analysis platform (TCMSP). The relevant targets of chronic cough were obtained from two databases: GeneCards and DrugBank. Take the intersection to get potential targets of SAD to treat chronic cough and establish the component-target regulatory network by CytoScape3.7.2 and protein-protein interaction (PPI) network by STRING 1.0. The function of the target gene and related pathways were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) in the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The significant pathways and their relevant targets were obtained and the target-pathway network was established by CytoScape3.7.2. Finally, molecular docking of the core active components and relevant targets was performed.Results: A total of 98 active components, 113 targets were identified. The component-target and target-pathway network of SAD and PPI network were established. Enrichment analysis of DAVID indicated that 2062 terms were in biological processes, 77 in cellular components, 142 in molecular functions and 20 significant pathways. In addition, the molecular docking showed that quercetin and luteolin had a good combination with the corresponding targets.Conclusions: It indicates that the active compounds of SAD, such as quercetin, luteolin, may act on AKT1, MAPK1, RELA, EGFR, BCL2 and regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications and Fluid shear stress and atherosclerosis pathway to exert the effects of anti-inflammatory, anti-airway remodeling, anti-oxidant stress and repair airway damage to treat chronic cough.

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Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma

10.21203/rs.3.rs-60894/v3 ◽

2021 ◽

Author(s):

Zhiqiang Chen ◽

Tong Lin ◽

Xiaozhong Liao ◽

Zeyun Li ◽

Ruiting Lin ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Signaling Pathway ◽

Experimental Results ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Components ◽

Active Compounds ◽

Apoptosis Rate

Abstract Background: Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods: By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results: 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusion:As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

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Investigating the Mechanism of Action of Frankincense against Drug-Induced Liver Injury Using Network Pharmacology and Molecular Docking

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210319160217 ◽

2021 ◽

Vol 18 ◽

Author(s):

Yu-cheng Liao ◽

Jing-wen Wang ◽

Qian Yang ◽

Wen-jun Wanga ◽

Chao Zhao ◽

...

Keyword(s):

Molecular Docking ◽

Liver Injury ◽

Mechanism Of Action ◽

Target Genes ◽

Network Pharmacology ◽

Active Components ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Pathway Enrichment ◽

Core Genes

Background: Frankincense has been used as a traditional medicine in many countries. It is an important herb with multiple targets and therapeutic effects including liver protection. However, its mechanism of action in drug-induced liver injury (DILI) remains unknown. Objective: The purpose of this work was to elucidate the active components, core genes, and molecular mechanism of frankincense in DILI through network pharmacology and molecular docking approaches. Method: The active components of frankincense and its target genes were obtained from the BATMAN-TCM database, and the DILI target genes were obtained from the GeneCards and DrugBank databases. Cytoscape was used to create the compound-shared gene target network. STRING and DAVID software were used to analyze key targets and pathway enrichment. Autodock Vina software was used for molecular docking. Results: Network analysis identified 16 compounds in frankincense and 103 target genes that are highly related to DILI. The core genes in the protein-protein interaction network are INS, IL6, TP53, TNF, SRC, PTGS2, IL1B, CAT, IL10, and IGF1. Furthermore, GO and KEGG pathway enrichment analyses indicated that the effect of frankincense on DILI is related to positive regulation of transcription from RNA polymerase II promoter and inflammatory response. Core pathways such as the HIF-1, TNF, FoxO, PI3K-Akt, and the sphingolipid signaling pathway are closely related to DILI. Conclusion: This study revealed the chemical constituents and pharmacological effects of frankincense and unveiled potential DILI healing targets. This study could provide insights for further development of drugs that specifically target DILI.

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Uncovering the Mechanism of the Effects of Pien-Tze-Huang on Liver Cancer Using Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4863015 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Shanghui Liu ◽

Run Wang ◽

Yan Lou ◽

Jia Liu

Keyword(s):

Molecular Docking ◽

Liver Cancer ◽

Molecular Mechanism ◽

Mechanism Of Action ◽

Network Pharmacology ◽

Active Ingredients ◽

The Core ◽

Molecular Mechanism Of Action ◽

Pien Tze Huang ◽

Core Genes

Pien-Tze-Huang (PTH) has a long history in the treatment of liver cancer. However, its molecular mechanism of action remains unclear. TCMSP and TCM were used to collect the active ingredients. Bioactive compounds targets were predicted by reverse pharmacophore models. The antiliver cancer targets of PTH were selected by gene comparison of liver cancer in the GEO database. Molecular docking was used to verify the binding activity of the targets and the active ingredients. The DAVID was used to analyze the gene function and signal pathway. A model was built with Cytoscape. The core genes were obtained by PPI network. We screened the 4 main medicinal ingredients of PTH to obtain 16 active ingredient, 190 potential targets, and 6 core genes. We found that active small molecules exert anticancer effects by multiple pathways. The core genes were involved in multiple biological processes. We also found that eight chemical components play a greater role in inhibiting liver cancer. PTH achieves the effect of inhibiting liver cancer through the synergistic effect of multiple components, multiple targets, and multiple pathways. This study provides a potential scientific basis for further elucidating the molecular mechanism of action of PTH against liver cancer.

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Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma

10.21203/rs.3.rs-60894/v2 ◽

2020 ◽

Author(s):

Zhiqiang Chen ◽

Tong Lin ◽

Xiaozhong Liao ◽

Zeyun Li ◽

Ruiting Lin ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Signaling Pathway ◽

Experimental Results ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Components ◽

Active Compounds ◽

Apoptosis Rate

Abstract Background This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC 50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC 50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusion As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effects through multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

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Screening of Potential Anti-Thrombotic Ingredients from Salvia miltiorrhiza in Zebrafish and by Molecular Docking

Molecules ◽

10.3390/molecules26226807 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6807

Author(s):

Huilan Tang ◽

Ningyi Qin ◽

Chang Rao ◽

Jiahui Zhu ◽

Haiqiang Wang ◽

...

Keyword(s):

Molecular Docking ◽

Salvia Miltiorrhiza ◽

In Vivo Model ◽

Dependent Manner ◽

Active Ingredients ◽

Active Components ◽

Vein Thrombosis ◽

Thrombosis Model ◽

Underlying Mechanisms

Background: Danshen (DS), the dry root of Salvia miltiorrhiza Bge., has been used in traditional Chinese medicine (TCM) for many years to promote blood circulation and to inhibit thrombosis. However, the active ingredients responsible for the anti-thrombotic effect and the underlying mechanisms are yet to be fully elucidated. Methods: Molecular docking was used to predict the active ingredients in DS and their potential targets by calculating the scores of docking between DS ingredients and thrombosis-related proteins. Then, a chemical-induced zebrafish thrombosis model was applied to confirm their anti-thrombotic effects. Result: The molecular docking results indicated that compared to the control ligand, higher docking scores were observed for several compounds in DS, among which salvianolic acid B (SAB), lithospermic acid (LA), rosmarinic acid (MA), and luteolin-7-O-β-d-glucoside (LG) could attenuate zebrafish caudal vein thrombosis and recover the decrease in heart red blood cells (RBCs) in a dose-dependent manner. Conclusions: Our study showed that it is possible to screen the potential active components in natural products by combining the molecular docking method and zebrafish in vivo model.

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Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma

Chinese Medicine ◽

10.1186/s13020-021-00423-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Zhiqiang Chen ◽

Tong Lin ◽

Xiaozhong Liao ◽

Zeyun Li ◽

Ruiting Lin ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Signaling Pathway ◽

Experimental Results ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Components ◽

Active Compounds ◽

Apoptosis Rate

Abstract Background Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusions As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

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The important herbal pair for the treatment of COVID-19 and its possible mechanisms

Chinese Medicine ◽

10.1186/s13020-021-00427-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Shujie Xia ◽

Zhangfeng Zhong ◽

Bizhen Gao ◽

Chi Teng Vong ◽

Xuejuan Lin ◽

...

Keyword(s):

Molecular Docking ◽

Association Rules ◽

Hypoxia Inducible Factor ◽

Mitogen Activated Protein Kinase ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Ingredients ◽

Active Components ◽

Ephedra Sinica ◽

Rule Approach

Abstract Background Coronavirus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicine (TCM) are effective in treating COVID-19. However, it is difficult to find the most effective combination herbal pair among numerous herbs, as well as identifying its potential mechanisms. Herbal pair is the main form of a combination of TCM herbs, which is widely used for the treatment of diseases. It can also help us to better understand the compatibility of TCM prescriptions, thus improving the curative effects. The purpose of this article is to explore the compatibility of TCM prescriptions and identify the most important herbal pair for the treatment of COVID-19, and then analyze the active components and potential mechanisms of this herbal pair. Methods We first systematically sorted the TCM prescriptions recommended by the leading experts for treating COVID-19, and the specific herbs contained in these prescriptions across different stages of the disease. Next, the association rule approach was employed to examine the distribution and compatibility among these TCM prescriptions, and then identify the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach, and analyzed the potential mechanisms against COVID-19. Finally, the main active compounds in the herbal pair were selected for molecular docking with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) 3CLpro and angiotensin converting enzyme II (ACE2) for further verification. Result We obtained 32 association rules for the herbal combinations in the selection of TCM treatment for COVID-19. The results showed that the combination of Amygdalus Communis Vas (ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value, as well as high support degree, which can be used in almost all the stages of COVID-19, so ACV and ESS (AE) were selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which might be related to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin, while the potential targets were Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1β (IL-1β), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA). The protein-protein interaction (PPI) cluster demonstrated that IL-6 was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The potential pathways mainly involved tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), and nucleotide-binding oligomerization domain (NOD)-like receptor (NLRs). The molecular docking results showed that the main active ingredients of AE have good affinity with SARS-COV-2 3CLpro and ACE2, which are consistent with the above analysis. Conclusions There were 32 association rules in the TCM prescriptions recommended by experts for COVID-19. The combination of ACV and EAS was the most important herbal pair for the treatment of COVID-19. AE might have therapeutic effects against COVID-19 by affecting the inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, targets and pathways.

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