scholarly journals Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Huangqin decoction on ulcerative Colitis

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Wu ◽  
Xinqiao Liu ◽  
Guiwei Li
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Topological Analysis ◽  
Therapeutic Targets ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Active Components

AbstractHuangqin decoction (HQD) is a Traditional Chinese Medicine formula for ulcerative colitis. However, the pharmacology and molecular mechanism of HQD on ulcerative colitis is still unclear. Combined microarray analysis, network pharmacology, and molecular docking for revealing the therapeutic targets and molecular mechanism of HQD against ulcerative colitis. TCMSP, DrugBank, Swiss Target Prediction were utilized to search the active components and effective targets of HQD. Ulcerative colitis effective targets were obtained by microarray data from the GEO database (GSE107499). Co-targets between HQD and ulcerative colitis are obtained by Draw Venn Diagram. PPI (Protein–protein interaction) network was constructed by the STRING database. To obtain the core target, topological analysis is exploited by Cytoscape 3.7.2. GO and KEGG enrichment pathway analysis was performed to Metascape platform, and molecular docking through Autodock Vina 1.1.2 finished. 161 active components with 486 effective targets of HQD were screened. 1542 ulcerative colitis effective targets were obtained with |Log2FC|> 1 and adjusted P-value < 0.05. The Venn analysis was contained 79 co-targets. Enrichment analysis showed that HQD played a role in TNF signaling pathway, IL-17 signaling pathway, Th17 cell differentiation, etc. IL6, TNF, IL1B, PTGS2, ESR1, and PPARG with the highest degree from PPI network were successfully docked with 19 core components of HQD, respectively. According to ZINC15 database, quercetin (ZINC4175638), baicalein (ZINC3871633), and wogonin (ZINC899093) recognized as key compounds of HQD on ulcerative colitis. PTGS2, ESR1, and PPARG are potential therapeutic targets of HQD. HQD can act on multiple targets through multi-pathway, to carry out its therapeutic role in ulcerative colitis.

Molecular Mechanism of The Effect of Huanglian Jiedu Decoction On Ulcerative Colitis Based On Network Pharmacology And Molecular Docking

2021 ◽  
Author(s):  
Jing Yang ◽  
Chao-Tao Tang ◽  
Ruiri Jin ◽  
Bixia Liu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Signal Pathway ◽  
Intestinal Barrier Function ◽  
Network Pharmacology ◽  
Bioactive Components ◽  
Ppi Network ◽  
Active Components

Abstract Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC by means of network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are considered to be very important to PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had good affinity with Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.

scholarly journals Network Pharmacology-Based Prediction of the Active Ingredients and Potential Targets of Chinese Herbal Danyu Gukang Pills for Application to Osteonecrosis of the Femoral Head Disease

2021 ◽  
Author(s):  
Yongchang Guo ◽  
Dapeng Zhang ◽  
Yuju Cao ◽  
Xiaoyan Feng ◽  
Caihong Shen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Femoral Head ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
In Vitro Experiments ◽  
Active Components

Abstract Ethnopharmacological relevanceOsteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide, which may lead to disability in patients without effective treatment. A newly developed formula of Chinese medicine, Danyu Gukang Pills (DGP), was recognized to be effective for ONFH. Nevertheless, its molecular mechanisms remain to be clarified. MethodsNetwork pharmacology was adopted to detect the mechanism of DGP on ONFH. The compounds of DGP were collected from the online databases, and active components were selected based on their OB and DL index. The potential proteins of DGP were acquired from TCMSP database, while the potential genes of ONFH were obtained from Gene Cards and Pubmed Gene databases. The function of Gene and potential pathways were researched by GO and KEGG pathway enrichment analysis. The compounds-targets and targets-pathways network were constructed in an R and Cytosacpe software. The mechanism was further investigated via molecular docking. Finally, in-vitro experiments were validated in the BMSCs. ResultsA total of 2305 compounds in DGP were gained, among which, 370 were selected as active components for which conforming to criteria. Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. ConclusionThe current study firstly researched the molecular mechanism of DGP on ONFH based on network pharmacology. The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway.

scholarly journals Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Kunyao Zhu ◽  
Man Zhang ◽  
Jia Long ◽  
Shuqi Zhang ◽  
Huali Luo
Keyword(s):  
Acute Pancreatitis ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Salvia Miltiorrhiza ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Regulation Of Transcription ◽  
Active Components ◽  
Positive Regulation

Using network pharmacology and molecular docking, this study investigated the molecular mechanisms by which the active components in Salvia miltiorrhiza can alleviate acute pancreatitis. Initially, the active components of Salvia miltiorrhiza and the targets collected from the GeneCards database were screened based on the platform of systematic pharmacology analysis of traditional Chinese medicine. Subsequently, the active components were intersected with the disease targets. Also, interactions among the targets were computed using the STRING database. Biological function and pathway enrichment were analyzed using the Cluster Profiler package in the R software. Protein-protein interaction and component target pathway network were constructed using the Cytoscape software. Ultimately, the key targets and their corresponding components in the network were verified using the AutoDock Vina software. The results showed Salvia miltiorrhiza had 111 targets for acute pancreatitis. The biological process (BP) analysis showed that the active components of Salvia miltiorrhiza induced a drug response, positive regulation of transcription by RNA polymerase II promoter, signal transduction, positive regulation of cell proliferation, and negative regulation of apoptosis. Furthermore, the KEGG enrichment analysis screened 118 ( P < 0.05 ) signaling pathways, such as the pathways related to cancer, neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, and cAMP signaling pathway, to name a few. Finally, molecular docking showed that the active components of Salvia miltiorrhiza had a good binding affinity with their corresponding target proteins. Through network pharmacology, this study predicted the potential pharmacodynamic material basis and the mechanisms by which Salvia miltiorrhiza can treat acute pancreatitis. Moreover, this study provided a scientific basis for mining the pharmacodynamic components of Salvia miltiorrhiza and expanding the scope of its clinical use.

scholarly journals Active Ingredients and Potential Mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against Ulcerative Colitis: A Network Pharmacology and Molecular Docking-Based Study

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ce Zhou ◽  
Hang Zhou ◽  
Furong Zhang ◽  
Liangliang Hao ◽  
Jing Guo
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Drug Targets ◽  
Target Genes ◽  
Network Pharmacology ◽  
Active Components ◽  
Therapeutic Principle ◽  
Pharmacological Mechanism ◽  
Egfr Signaling Pathway

Background. Ulcerative colitis (UC), a chronic and nonspecific inflammatory bowel disease, seriously affects the quality of patients’ life. Han Re Bing Yong Fa (treating diseases with both cool- and warm-natured herbs) is a classical therapeutic principle of traditional Chinese medicine (TCM), which is often used to treat chronic diseases, including UC. The Gan Jiang-Huang Qin-Huang Lian-Ren Shen decoction (GJHQHLRSD), a representative of Han Re Bing Yong Fa, is effective in alleviating inflammatory symptoms in UC. However, the pharmacological mechanism underlying its anti-inflammatory effect remains unclear. Methods. A network pharmacology strategy, including the construction and analysis of the drug–disease network, was used to explore the complex mechanism of GJHQHLRSD treatment of UC. In addition, molecular docking technology was used to preliminarily examine the binding ability of the potential active components and core therapeutic targets of GJHQHLRSD. Results. The network pharmacology results revealed 140 targets of GJHQHLRSD which are involved in UC. The PPI network analysis identified seven target genes: BCL2L1, NR3C1, ALOX5, S1PR5, NR1I2, CYP2D6, and LPAR6. The molecular docking results revealed that the following displayed strongest combined effects: EGFR with kaempferol, ERK1 with worenine, STAT3 with Palmidin A, BCL2L1 with diop and VEGFA with ginsenoside Rg3. The KEGG and gene ontology enrichment analyses results indicated that GJHQHLRSD functions by regulating the EGFR signaling pathway in UC treatment. Other effective biological processes involved in UC treatment included cancer-related as well as inflammation and viral infection signaling pathways, such as the “MicroRNAs in cancer,” “TNF signaling pathway,” and “JAK-STAT signaling pathway.” Conclusions. This study reflects the multicomponent, multitarget, and multipathway characteristics of the action mechanism of GJHQHLRSD in treating UC. Furthermore, it helps better understand the TCM therapeutic principle of Han Re Bing Yong Fa and explore novel candidate drug targets for UC treatment.

scholarly journals Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

2020 ◽  
Vol 2020 ◽  
pp. 1-24
Author(s):  
Bei Yin ◽  
Yi-Ming Bi ◽  
Guan-Jie Fan ◽  
Ya-Qing Xia
Keyword(s):  
Molecular Docking ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Binding Capacity ◽  
Topological Analysis ◽  
Herbal Medicines ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Active Components ◽  
Ppi Networks

Background. Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Methods. Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. Results. There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Conclusion. Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.

scholarly journals Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Yan-gu Tao ◽  
Xiu-Fang Huang ◽  
Jun-yan Wang ◽  
Meng-ru Kang ◽  
Ling-jun Wang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Diabetic Complications ◽  
Interaction Network ◽  
Clinical Syndrome ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Target Network

Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.

scholarly journals Based on Network Pharmacology to Explore the Molecular Targets and Mechanisms of Gegen Qinlian Decoction for the Treatment of Ulcerative Colitis

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Meiqi Wei ◽  
He Li ◽  
Qifang Li ◽  
Yi Qiao ◽  
Qun Ma ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Genes ◽  
Topological Analysis ◽  
Molecular Targets ◽  
Enrichment Analysis ◽  
Binding Activity ◽  
Network Pharmacology ◽  
Active Ingredients

Background. Gegen Qinlian (GGQL) decoction is a common Chinese herbal compound for the treatment of ulcerative colitis (UC). In this study, we aimed to identify its molecular target and the mechanism involved in UC treatment by network pharmacology and molecular docking. Material and Methods. The active ingredients of Puerariae, Scutellariae, Coptis, and Glycyrrhiza were screened using the TCMSP platform with drug ‐ like   properties   DL ≥ 0.18 and oral   availability   OB ≥ 30 % . To find the intersection genes and construct the TCM compound-disease regulatory network, the molecular targets were determined in the UniProt database and then compared with the UC disease differential genes with P value < 0.005 and ∣ log 2   fold   change ∣ > 1 obtained in the GEO database. The intersection genes were subjected to protein-protein interaction (PPI) construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After screening the key active ingredients and target genes, the AutoDock software was used for molecular docking, and the best binding target was selected for molecular docking to verify the binding activity. Results. A total of 146 active compounds were screened, and quercetin, kaempferol, wogonin, and stigmasterol were identified as the active ingredients with the highest associated targets, and NOS2, PPARG, and MMP1 were the targets associated with the maximum number of active ingredients. Through topological analysis, 32 strongly associated proteins were found, of which EGFR, PPARG, ESR1, HSP90AA1, MYC, HSPA5, AR, AKT1, and RELA were predicted targets of the traditional Chinese medicine, and PPARG was also an intersection gene. It was speculated that these targets were the key to the use of GGQL in UC treatment. GO enrichment results showed significant enrichment of biological processes, such as oxygen levels, leukocyte migration, collagen metabolic processes, and nutritional coping. KEGG enrichment showed that genes were particularly enriched in the IL-17 signaling pathway, AGE-RAGE signaling pathway, toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, transcriptional deregulation in cancer, and other pathways. Molecular docking results showed that key components in GGQL had good potential to bind to the target genes MMP3, IL1B, NOS2, HMOX1, PPARG, and PLAU. Conclusion. GGQL may play a role in the treatment of ulcerative colitis by anti-inflammation, antioxidation, and inhibition of cancer gene transcription.

scholarly journals Network Pharmacology-Based Approach to Investigate the Molecular Targets of Rhubarb for Treating Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Lan Jiang ◽  
Zhongquan Shi ◽  
Yi Yang
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Protein Interactions ◽  
Scientific Basis ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Active Components ◽  
Kegg Pathways

Background. As a traditional Chinese medicine, rhubarb (also named Dahuang) is used to treat various diseases. Objective. To explore the possible antitumor mechanism of rhubarb by using network pharmacology and molecular docking in this study. Methods. Bioactive ingredients and related targets of rhubarb were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. And the gene names corresponding to the proteins were found in the UniProt database. Then, the tumor-related targets were screened out from GeneCards and OMIM databases. Key antitumor targets of rhubarb were acquired by overlapping the above targets via the Venn diagram. The antitumor targets network of rhubarb active components was constructed by using Cytoscape 3.6.0 software. The protein interactions network was constructed using the STRING database. The GO and KEGG pathways involved in the targets were analyzed by using the DAVID database. Autodock Vina software was used to verify the molecular docking of rhubarb components and key targets. Results. Through screening and analysis, 10 active ingredients and 58 antitumor prediction targets were obtained and constructed a compound-target network. The targets such as CASP3, JUN, MYC, TNF, and PTGS2 may play a crucial role. These targets are involved in cancer pathway, calcium signaling pathway, cell apoptosis, small-cell lung cancer pathway, p53 signaling pathway, and TNF signaling pathway. The docking results indicated that the rhein binding with the CASP3 showed the highest binding energy. Conclusion. Based on the network pharmacology, the characteristics of multicomponent, multitarget, and multipathway of rhubarb were discussed, which provided a scientific basis for explaining the mechanism in treating cancer and new ideas for further research.

scholarly journals Molecular mechanism underlying the hypolipidemic effect of Shanmei Capsule based on network pharmacology and molecular docking

2021 ◽  
Vol 29 ◽  
pp. 239-256
Author(s):  
Qian Wang ◽  
Lijing Du ◽  
Jiana Hong ◽  
Zhenlin Chen ◽  
Huijian Liu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Kegg Pathway ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Hypolipidemic Effect ◽  
Active Ingredients ◽  
Pathway Enrichment

BACKGROUND: Shanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed. OBJECTIVE: To elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking. METHODS: Active ingredients, targets of Shanmei Capsule as well as targets for hyperlipidemia were screened based on database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 database. Ingredient-target-disease-pathway network was visualized utilizing Cytoscape software and molecular docking was performed by Autodock Vina. RESULTS: Seventeen active ingredients in Shanmei Capsule were screened out with a closely connection with 34 hyperlipidemia-related targets. GO analysis revealed 40 biological processes, 5 cellular components and 29 molecular functions. A total of 15 signal pathways were enriched by KEGG pathway enrichment analysis. The docking results indicated that the binding activities of key ingredients for PPAR-α are equivalent to that of the positive drug lifibrate. CONCLUSIONS: The possible molecular mechanism mainly involved PPAR signaling pathway, Bile secretion and TNF signaling pathway via acting on MAPK8, PPARγ, MMP9, PPARα, FABP4 and NOS2 targets.

scholarly journals NMPA-approved traditional Chinese medicine-Pingwei Pill: new indication for colistin recovery against MCR-positive bacteria infection

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qiushuang Sheng ◽  
Runbao Du ◽  
Cunhui Ma ◽  
Yonglin Zhou ◽  
Xue Shen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Bacterial Infection ◽  
Molecular Mechanisms ◽  
Topological Analysis ◽  
Network Pharmacology ◽  
Synergistic Activity ◽  
Colistin Resistance ◽  
Western Blot Assay ◽  
Gram Negative

Abstract Background The wide spread of plasmid-mediated colistin resistance by mobile colistin resistance (MCR) in Enterobacteriaceae severely limits the clinical application of colistin as a last-line drug against bacterial infection. The identification of colistin potentiator from natural plants or their compound preparation as antibiotic adjuncts is a new promising strategy to meet this challenge. Methods Herein, the synergistic activity, as well as the potential mechanism, of Pingwei pill plus antibiotics against MCR-positive Gram-negative pathogens was examined using checkerboard assay, time-killing curves, combined disk test, western blot assay, and microscope analysis. Additionally, the Salmonella sp. HYM2 infection models of mouse and chick were employed to examine the in vivo efficacy of Pingwei pill in combination with colistin against bacteria infection. Finally, network pharmacology and molecular docking assay were used to predicate other actions of Pingwei pill for Salmonella infection. Results Our results revealed that Pingwei Pill synergistically potentiated the antibacterial activity of colistin against MCR-1-positive bacteria by accelerating the damage and permeability of the bacterial outer membrane with an FIC (Fractional Inhibitory Concentration) index less than 0.5. The treatment of Pingwei Pill neither inhibited bacterial growth nor affected MCR production. Notably, Pingwei Pill in combination with colistin significantly prolonged the median survival in mouse and chick models of infection using the Salmonella sp. strain HYM2, decreased bacteria burden and organ index of infected animal, alleviated pathological damage of cecum, which suggest that Pingwei Pill recovered the therapeutic performance of colistin for MCR-1- positive Salmonella infection in mice and the naturally infected host chick. Pharmacological network topological analysis, molecular docking, bacterial adhesion, and invasion pathway verification assays were performed to identify the other molecular mechanisms of Pingwei Pill as a colistin potentiator against Gram-negative bacteria infection. Conclusion Taken together, NMPA (National Medical Products Administration)-approved Pingwei Pill is a promising adjuvant with colistin for MCR-positive bacterial infection with a shortened R&D (research and development) cycle and affordable R&D cost and risk.

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