Network Pharmacology Analysis Research Articles

Network Pharmacology Approach to Understanding the Antidiabetic Effects of Pineapple Peel Hexane Extract

The increased interest in exploring alternative treatments for type 2 diabetes mellitus is accompanied by a rise in the prevalence of type 2 diabetes mellitus. Pineapple peel is one of the by-products of pineapple fruit and is known to possess potential for anti-diabetic activity. In this study, the n-hexane extract of pineapple peel was analyzed using network pharmacology methods to ascertain its potential in treating type 2 diabetes mellitus. The GC-MS analysis of the n-hexane extract of pineapple peel revealed the presence of 42 compounds, with 8 of them considered safe as they met the Lipinski Rule of Five criteria for drug-likeness and were classified as safe with toxicity levels in classes IV and V. The pineapple peel extract targeted 55 proteins related to type 2 diabetes mellitus (DMT2), potentially affecting DMT2 through the AGE-RAGE pathway in diabetes complications and insulin resistance. Network pharmacology analysis identified five genes targeted by pineapple peel, namely MAPK1, JAK2, MAPK8, PRKCD, and PPARA. Among these genes, MAPK1 exhibited a higher overall score than the others. Apart from its role in diabetes, MAPK1 is also implicated in cancer.

Resveratrol ameliorates glioblastoma inflammatory response by reducing NLRP3 inflammasome activation through inhibition of the JAK2/STAT3 pathway

ObjectivesThe aim of this study was to investigate the anti-tumor effect of resveratrol (RSV) on glioblastoma (GBM) and its specific mechanism in improving the inflammatory response of the tumor microenvironment. The tumor microenvironment of GBM is highly neuroinflammatory, inducing tumor immunosuppression. Therefore, ameliorating the inflammatory response is an important focus for anti-tumor research.MethodsThe anti-tumor effect of RSV on GBM was demonstrated through in vitro cellular assays, including CCK-8, EdU, PI staining, Transwell, wound healing assay, and flow cytometry. Potential mechanisms of RSV's anti-GBM effects were identified through network pharmacological analysis. In addition, the relationship of RSV with the JAK2/STAT3 signaling pathway and the inflammasome NLRP3 was verified using Western blot.ResultsRSV significantly inhibited cell viability in GBM cell lines LN-229 and U87-MG. Furthermore, it inhibited the proliferation and invasive migration ability of GBM cells, while promoting apoptosis. Network pharmacological analysis revealed a close association between the anti-GBM effects of RSV and the JAK/STAT signaling pathway, as well as inflammatory responses. Western blot analysis confirmed that RSV inhibited the over-activation of the inflammasome NLRP3 through the JAK2/STAT3 signaling pathway. Partial reversal of RSV's inhibition of inflammasome NLRP3 was observed with the addition of the JAK/STAT agonist RO8191.ConclusionsIn vitro, RSV can exert anti-tumor effects on GBM and improve the inflammatory response in the GBM microenvironment by inhibiting the activation of the JAK2/STAT3 signaling pathway. These findings provide new insights into potential therapeutic targets for GBM.

Exploration of anti-diabetic activity and metabolite profiling of Bruguiera cylindrica (l.) Bl.-in vivo anti-diabetic activity, exploration of molecular mechanism, and network pharmacological analysis.

The Bruguiera cylindrica L. is a mangrove plant that is typically found in coastal areas of Asia, including India. It has been known for its medicinal properties, which have been utilized for generations. For example, in Thailand, it has been used to treat wounds and diarrhoea, while in India, it has been effective in addressing diabetes, ulcers, and other health issues. This particular study sought to investigate the potential of B. cylindrica bark extract in reducing the symptoms of diabetes in rats. In this study, we examined the potential of B. cylindrica bark extract as an inhibitor of α-amylase and α-glucosidase enzymes in vitro. We also evaluated the effects of the extract and Metformin on rats fed high-fat diets and measured their lipid profiles and biochemical parameters. Furthermore, we conducted a network pharmacology analysis to identify proteins and pathways involved in the amelioration of diabetes. Through metabolite profiling, we identified 58 compounds in B. cylindrica hydroalcoholic extract. These compounds include alkaloids, phenolics, flavonoids, and fatty acids. The extract was found to have a dose-dependent inhibition activity against α-amylase and α-glucosidase, with IC50 values similar to acarbose. In rats, oral administration of 200-400mg/kg of B. cylindrica led to reduced blood glucose levels and normalized serum biochemical parameters. Bruguiera cylindrica bark may reduce blood sugar levels in rats with diabetes. The study found metabolites that interact with protein targets associated with different types of diabetes.

Potential Mechanism of Tibetan Medicine Liuwei Muxiang Pills against Colorectal Cancer: Network Pharmacology and Bioinformatics Analyses.

This study aimed to explore the mechanism through which Tibetan medicine Liuwei Muxiang (LWMX) pills acts against colorectal cancer (CRC). We firstly retrieved the active ingredients and the correlated targets of LWMX pills from public databases. The CRC-related targets were determined through bioinformatic analysis of a public CRC dataset. By computing the intersection of the drug-specific and disease-related targets, LWMX pill-CRC interaction networks were constructed using the protein-protein interaction (PPI) method and functional enrichment analysis. Subsequently, we determined the hub genes using machine learning tools and further verified their critical roles in CRC treatment via immune infiltration analysis and molecular docking studies. We identified 81 active ingredients in LWMX pills with 614 correlated targets, 1877 differentially expressed genes, and 9534 coexpression module genes related to CRC. A total of 5 target hub genes were identified among the 108 intersecting genes using machine learning algorithms. The immune infiltration analysis results suggested that LWMX pills could affect the CRC immune infiltration microenvironment by regulating the expression of the target hub genes. Finally, the molecular docking outcomes revealed stable binding affinity between all target hub proteins and the primary active ingredients of LWMX pills. Our findings illustrate the anti-CRC potential and the mechanism of action of LWMX pills and provide novel insights into multitarget medication for CRC treatment.

Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis

Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein–protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP.

Bajitianwan formula extract ameliorates bone loss induced by iron overload via activating RAGE/PI3K/AKT pathway based on network pharmacology and transcriptomic analysis.

Osteoporosis (OP) is closely related to iron overload. Bajitianwan (BJTW) is a traditional Chinese medicine formulation used for treating senile diseases such as dementia and osteoporosis. Modern pharmacological researches have found that BJTW has beneficial effect on bone loss and memory impairment in aging rats. This paper aimed to explore the role and mechanism of BJTW in ameliorating iron overload-induced bone loss. Furthermore, BJTW effectively improved the bone micro-structure of the femur in mice, and altered bone metabolism biomarkers alkaline phosphatase (ALP) and osteocalcin (OCN) in serum, as well as oxidative indexes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) glutathione (GSH) and malondialdehyde (MDA) in liver. As for network pharmacology, 73 components collected from BJTW regulated 99 common targets merged in the BJTW and OP. The results of RNA-seq indicated that there were 418 potential targets in BJTW low dose group (BJTW-L) and 347 potential targets in BJTW high dose group (BJTW-H). Intriguingly, both PI3K-AKT signaling pathway and the AGEs-RAGE signaling pathway were contained in the KEGG pathways enrichment results of network pharmacology and transcriptomics, which were considered as the potential mechanism. Additionally, we verified that BJTW regulated the expression of related proteins in RAGE/PI3K-AKT pathways in MC3T3-E1 cells. In summary, BJTW has potent effect on protecting against iron overload-induced OP, and its mechanism may be related to the activation of the RAGE/PI3K-AKT signaling pathways.

Xiaoer niuhuang qingxin powder alleviates influenza a virus infection by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway

Ethnopharmacological relevanceXiaoer Niuhuang Qingxin Powder (XNQP) is a classic traditional Chinese medicine formula with significant clinical efficacy for treating febrile convulsions and influenza. Aim of the studyThis study aims to explore the potential mechanisms of XNQP in combating combating the influenza A virus, providing a theoretical basis for its clinical application. Materials and methodsThe present investigation employed network pharmacology and bioinformatics analysis to determine the TLR4/MyD88/NF-κB signaling pathway as a viable target for XNQP intervention in IAV infection.Subsequently, a mouse model of influenza A virus infection was established, and different doses of XNQP were used for intervention. The protein expression levels of TLR4/MyD88/NF-κB were detected using HE staining, Elisa, immunohistochemistry, immunofluorescence, and western blot. ResultsThe results showed that treatment with XNQP after IAV infection reduced the mortality and prolonged the survival time of infected mice. It reduced the release of TNF-α and IFN-γ in the serum and alleviated pathological damage in the lung tissue following infection. Additionally, the levels of TLR4, MyD88, NF-κB, and p–NF–κB P65 proteins were significantly reduced in lung tissue by XNQP. The inhibitory effect of XNQP on the expression of MyD88 and NF-κB was antagonized when TLR4 signaling was overexpressed. Consequently, the expression levels of MyD88, NF-κB, and p–NF–κB P65 were increased in lung tissue. Conversely, the expression levels of the proteins MyD88, NF-κB, and p–NF–κB P65 were downregulated when TLR4 signaling was inhibited. ConclusionsXNQP alleviated lung pathological changes, reduced serum levels of inflammatory factors, reduced mortality, and prolonged survival time in mice by inhibiting the overexpression of the TLR4/MyD88/NF-κB signaling pathway in lung tissues after IAV infection.

Metabolomic Profiling of Leptadenia reticulata: Unveiling Therapeutic Potential for Inflammatory Diseases through Network Pharmacology and Docking Studies.

Medicinal plants have been utilized since ancient times for their therapeutic properties, offering potential solutions for various ailments, including epidemics. Among these, Leptadenia reticulata, a member of the Asclepiadaceae family, has been traditionally employed to address numerous conditions such as diarrhea, cancer, and fever. In this study, employing HR-LCMS/MS(Q-TOF) analysis, we identified 113 compounds from the methanolic extract of L. reticulata. Utilizing Lipinski's rule of five, we evaluated the drug-likeness of these compounds using SwissADME and ProTox II. SwissTarget Prediction facilitated the identification of potential inflammatory targets, and these targets were discerned through the Genecard, TTD, and CTD databases. A network pharmacology analysis unveiled hub proteins including CCR2, ICAM1, KIT, MPO, NOS2, and STAT3. Molecular docking studies identified various constituents of L. reticulata, exhibiting high binding affinity scores. Further investigations involving in vivo testing and genomic analyses of metabolite-encoding genes will be pivotal in developing efficacious natural-source drugs. Additionally, the potential of molecular dynamics simulations warrants exploration, offering insights into the dynamic behavior of protein-compound interactions and guiding the design of novel therapeutics.

Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation.

Background and purpose: The Bushenyiqi decoction (BYD), a contemporary prescription of traditional Chinese medicine (TCM), has been observed to significantly ameliorate asthma symptoms in patients based on clinical observations. Although multi-component and multi-target characteristics are important attributes of BYD treatment, its pharmacological effect on asthma and the underlying mechanism of action remain unclear. Method: Network pharmacology: the asthma-related genes were retrieved from the GeneCards and OMIM database. The active constituents of BYD and their corresponding target genes were collected from the TCMSP database. The underlying pathways associated with overlapping targets between BYD and asthma were identified through GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Experimental validation: pulmonary function tests, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson's trichrome stainings were conducted to validate the efficacy of BYD in ameliorating airway inflammation in allergic asthma mice. Western blot (WB) and molecular docking were performed to confirm the involvement of the underlying pathway in BYD treatment of asthma. Results: The results of animal experiments demonstrated that BYD may improve airway responsiveness and suppress airway inflammation in allergic asthma mice. The network pharmacological analysis revealed the involvement of 11 potentially key active components, 9 potential key targets, and the phosphatidylinositol3 kinase-RAC-α serine/threonine-protein kinase (PI3K/AKT) signaling pathway in the mechanism of action of BYD for asthma treatment. Our findings have confirmed that BYD effectively alleviated airway inflammation by targeting interleukin 6 (IL-6), epidermal growth factor receptor (EGFR), and hypoxia inducible factor 1 alpha (HIF1A), with quercetin, kaempferol, and luteolin performing as the pivotal active constituents. BYD may potentially reduce inflammatory cell infiltration in lung tissues by regulating the PI3K/AKT signaling pathway. Conclusion: In conclusion, the integration of network pharmacology and biological experiments has demonstrated that key constituents of BYD, such as quercetin, kaempferol, and luteolin, exhibit targeted effects on IL-6, EGFR, and HIF1A in combating asthma-related inflammation through inhibition of the PI3K/AKT signaling pathway. The findings of this investigation provide evidence supporting the effectiveness of TCM's "bushenyiqi" therapy in asthma management, as corroborated by contemporary medical technology.

Mechanism of acacetin regulating hepatic stellate cell apoptosis based on network pharmacology and experimental verification

BackgroundHepatic fibrosis is caused by various liver diseases and eventually develops into liver cancer. There is no specific drug approved for the treatment of hepatic fibrosis in the world. Acacetin (AC), a natural flavonoid, is widely present in nature in various plants, such as black locust, Damiana, Silver birch. It has been reported that acacetin can inhibit the proliferation of cancer cells and induce apoptosis. PurposeIn this study, we investigated the effect of acacetin on hepatic stellate cell apoptosis, thereby improving hepatic fibrosis, and combined experimental validation and molecular docking to reveal the underlying mechanism. ResultFirst, we discovered that acacetin inhibited hepatic stellate cell proliferation as well as the expression of fibrosis-related proteins α-smooth muscle actin (α-SMA) and collagen type I 1 gene (COL1A1) in LX2 cells. Acacetin was then found to promote apoptosis of hepatic stellate cells through the caspase cascade pathway. Network pharmacology screening showed that TP53, CASP3, CASP8, BCL2, PARP1, and BAX were the most important targets related to apoptosis in the PPI network. GO and KEGG analyses of these six important targets were performed, and the top 10 enriched biological processes and related signaling pathways were revealed. Further network pharmacology analysis proved that apoptosis was involved in the biological process of acacetin's action against hepatic stellate cells. Finally, molecular docking revealed that acacetin binds to the active sites of six apoptotic targets. In vitro experiments further confirmed that acacetin could promote the apoptosis of LX2 cells by inducing the activation of P53, thereby improving hepatic fibrosis. Conclusionacacetin induces P53 activation and promotes apoptosis of hepatic stellate cells thereby ameliorating hepatic fibrosis.

Effects of Tibetan medicine Longdan zhike tablet on chronic obstructive pulmonary disease through MAPK pathway

Ethnopharmacological relevanceLongdan zhike tablet (LDZK) is a Tibetan medicine formula commonly used in the highland region of Tibet, China, to ameliorate respiratory diseases, such as acute bronchitis and asthma. In Chinese traditional medicine, some herbal formulas with anti-inflammatory properties targeting the respiratory system are clinically adopted as supplementary therapies for chronic obstructive pulmonary disease (COPD). However, the specific anti-COPD effects of LDZK remain to be evaluated. Aim of the studyThe aim of this study is to identify the principal bioactive compounds in LDZK, and elucidate the effects and mechanisms of the LDZK on COPD. MethodsHigh-resolution mass spectrometry was utilized for a comprehensive characterization of the chemical composition of LDZK. The therapeutic effects of LDZK were assessed on the LPS-papain-induced COPD mouse model, and LPS-induced activation model of A549 cells. The safety of LDZK was evaluated by orally administering a single dose of 30 g/kg to rats and monitoring physiological and biochemical indicators after a 14-day period. Network pharmacology and Western blot analysis were employed for mechanism prediction of LDZK. ResultsA comprehensive analysis identified a total of 45 compounds as the major constituents of LDZK. Oral administration of LDZK resulted in notable ameliorative effects in respiratory function, accompanied by reduced inflammatory cell counts and cytokine levels in the lungs of COPD mice. Acute toxicity tests demonstrated a favorable safety profile at a dose equivalent to 292 times the clinically prescribed dose. In vitro studies revealed that LDZK exhibited protective effects on A549 cells by mitigating LPS-induced cellular damage, reducing the release of NO, and downregulating the expression of iNOS, COX2, IL-1β, IL-6, and TNF-α. Network pharmacology and Western blot analysis indicated that LDZK primarily modulated the MAPK signaling pathway and inhibited the phosphorylation of p38/ERK/JNK. ConclusionsLDZK exerts significant therapeutic effects on COPD through the regulation of the MAPK pathway, suggesting its potential as a promising adjunctive therapy for the treatment of chronic inflammation in COPD.

Exploration of anti-osteoporotic peptides from Moringa oleifera leaf proteins by network pharmacology, molecular docking, molecular dynamics and cellular assay analyses

Moringa oleiferaleaf peptide, which is a plant-derived bioactive peptide, exhibits several advantages, including safety, high efficiency and nontoxic side effects. The goal of this study was to identify representative antiosteoporotic peptides fromMoringa oleiferaleaf proteins and determine their regulatory mechanisms using network pharmacology, molecular docking and molecular dynamics. The following core targets of Moringa oleifera leaf antiosteoporotic peptides were screened by network pharmacology: SRC, MAPK1, JUN and STAT3. Through molecular docking, DPYLGK was identified as a representative active peptide from the Moringa oleifera leaf protein, and SRC was determined to be a potential primary target. Molecular dynamics revealed the intermolecular mechanism of DPYLGK and SRC. Cellular assays showed that DPYLGK promotes bone formation and inhibits bone resorption. These findings demonstrated that DPYLGK is an anti-osteoporotic peptide with dual regulatory effects and will aid in the development of functional foods to prevent osteoporosis.

Solamargine improves the therapeutic efficacy of anti-PD-L1 in lung adenocarcinoma by inhibiting STAT1 activation

ObjectiveThe effect of solamargine on lung adenocarcinoma and its effect on STAT1 signaling pathway mediated immune escape were studied through network pharmacology and in vitro and in vivo experiments. MethodsThe solamargine targets were screened using the TCMSP and the LUAD targets were screened using the GeneCard, OMIM, PharmGkb, TTD and DrugBank databases. PPI network analysis and target prediction were performed using GO and KEGG. Colony formation assay, EDU staining, wound healing, transwell assay, Hoechst and flow cytometry were used to detect the effects of solamargine on the proliferation, migration and apoptosis of LUAD. Western blotting (WB) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect P-STAT1 and PD-L1 expression. And immunofluorescence was used to detect P-STAT1 expression. In vivo experiments, C57BL/6 mice were divided into control group, low concentration group, high concentration group, positive control group and combination group. Every other day, following seven consecutive doses, the size of the tumor was assessed. Finally, the expressions of P-STAT1, STAT1, PD-L1 and apoptosis index proteins were detected by WB. ResultsThe anti-LUAD effect of solamargine was found by wound healing, colony formation assay, transwell assay, hoechst and EdU staining. The results of network pharmacological analysis showed that solamargine could suppress STAT1 expression level. Further enrichment assay of STAT1 showed that STAT1 was associated with immune-related pathways. In addition, molecular signal analysis by WB and RT-qPCR indicated that solamargine could reduce the expression levels of P-STAT1 and PD-L1 in a concentration-dependent manner. According to the results of in vivo assays, combination of solamargine and immune checkpoint inhibitors (ICIs) durvalumab could significantly inhibit the growth of Lewis transplanted tumors in C57BL/6 mice, and no toxic side effect was recoded. ConclusionThese results indicated that solamargine could inhibit the proliferation and promote the apoptosis of LUAD. It also could reduce the expression level of P-STAT1 protein and inhibit the expression level of PD-L1. At the same time, the combination with the ICIs can better block the expression of PD-L1 in cells, thereby inhibiting the immune escape pathway of tumor cells and achieving anti-tumor effects. This study proposed a novel combined therapeutic approach, involving the inhibition of STAT1 by solamargine in conjunction with ICIs.

1-Ethoxycarbonyl-beta-carboline inhibits the M2 polarization of tumor-associated macrophages: A study based on network pharmacology and molecular docking analyses

AimThrough network pharmacology, molecular docking, molecular dynamics in combination with experimentation, we explored the mechanism whereby 1-ethoxycarbonyl-beta-carboline (EBC) regulates the M2 polarization of tumor-associated macrophages. MethodsNetwork pharmacology was adopted for analyzing the targets and signaling pathways related to the M2 polarization of EBC-macrophages, small molecular-protein docking was employed to analyze the possibility of EBC bonding to related protein, and molecular dynamics was introduced to analyze the binding energy between EBC and HDAC2. The M2 polarization of RAW264.7 macrophages was triggered in vitro by IL-4. After EBC intervention, the expressions of M1/M2 polarization-related cytokines were detected, and the mechanism of EBC action was explored in HDAC2-knockout RAW264.7 macrophages. A tumor-bearing mouse model was established in vitro to find the impact of EBC on tumor-associated M2 macrophages. ResultsAs revealed by the network pharmacology, molecular docking and molecular dynamics analyses, EBC was associated with 51 proteins, including HDAC2, NF-κB and HDAC4. Molecular docking and dynamics analyses suggested that HDAC2 was the main target of EBC. In vitro experiments discovered that EBC could hinder the M2 polarization of RAW264.7 macrophages, which exerted insignificant effect on the M1-associated cytokines, but could lower the levels of M2-associated cytokines. After knocking out HDAC2, EBC could not further inhibit the M2 polarization of macrophages. At the mouse level, EBC could hinder the tumor growth and the tissue levels of M2 macrophages, whose effect was associated with HDAC2. ConclusionOur study combining multiple methods finds that EBC inhibits the HDAC2-mediated M2 polarization of macrophages, thereby playing an anti-tumor role.

TCMNPAS: a comprehensive analysis platform integrating network formulaology and network pharmacology for exploring traditional Chinese medicine

The application of network formulaology and network pharmacology has significantly advanced the scientific understanding of traditional Chinese medicine (TCM) treatment mechanisms in disease. The field of herbal biology is experiencing a surge in data generation. However, researchers are encountering challenges due to the fragmented nature of the data and the reliance on programming tools for data analysis. We have developed TCMNPAS, a comprehensive analysis platform that integrates network formularology and network pharmacology. This platform is designed to investigate in-depth the compatibility characteristics of TCM formulas and their potential molecular mechanisms. TCMNPAS incorporates multiple resources and offers a range of functions designed for automated analysis implementation, including prescription mining, molecular docking, network pharmacology analysis, and visualization. These functions enable researchers to analyze and obtain core herbs and core formulas from herbal prescription data through prescription mining. Additionally, TCMNPAS facilitates virtual screening of active compounds in TCM and its formulas through batch molecular docking, allowing for the rapid construction and analysis of networks associated with “herb-compound-target-pathway” and disease targets. Built upon the integrated analysis concept of network formulaology and network pharmacology, TCMNPAS enables quick point-and-click completion of network-based association analysis, spanning from core formula mining from clinical data to the exploration of therapeutic targets for disease treatment. TCMNPAS serves as a powerful platform for uncovering the combinatorial rules and mechanism of TCM formulas holistically. We distribute TCMNPAS within an open-source R package at GitHub (https://github.com/yangpluszhu/tcmnpas), and the project is freely available at http://54.223.75.62:3838/.

Prediction of potential mechanisms of rhubarb therapy for colorectal cancer based on network pharmacological analysis and molecular docking.

The objective of this study was to investigate the potential targets and mechanism of Rheum palmatum L in the treatment of colorectal cancer based on the network pharmacology and molecular docking, which could provide the theoretical basis for clinical applications. The potential components were screened using TCMSP database and articles. The gene targets of colorectal cancer were screened through the Genecards database and Online Mendelian Inheritance in Man database. Then, the common targets of components and colorectal cancer were used to construct the network diagram of active components and targets in Cytoscape 3.7.0. The protein-protein interaction (PPI) diagram was generated using String database, and the targets were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular docking between gene targets and active components was analyzed via AutoDock, and visualized through PyMol. Among this study, main targets might be TP53, EGF, MYC, CASP3, JUN, PTGS2, HSP90AA1, MMP9, ESR1, PPARG. And 10 key elements might associate with them, such as aloe-emodin, beta-sitosterol, gallic acid, eupatin, emodin, physcion, cis-resveratrol, rhein, crysophanol, catechin. The treatment process was found to involve nitrogen metabolism, p53 signaling pathway, and various cancer related pathway, as well as the AGE-RAGE signaling pathway, estrogen signaling pathway, interleukin-17 signaling pathway and thyroid hormone signaling pathway. The molecular docking was verified the combination between key components and their respective target proteins. Network pharmacological analysis demonstrated that R palmatum was could regulated p53, AGE-RAGE, interleukin-17 and related signaling pathway in colorectal cancer, which might provide a scientific basis of mechanism.

Integrating metabolomics and network pharmacology to assess the effects of Mahuang Xixin Fuzi decoction on migraine rats induced by nitroglycerin.

This study was designed to investigate the pharmacological activity and therapeutic mechanism of Mahuang Xixin Fuzi decoction (MXFD) on migraine. Migraine model rats induced by nitroglycerin were established, and then orally administered with MXFD for 7 days. Blood and urine samples were collected to identify differential metabolites with metabolomics. To integrate the findings from network pharmacology and metabolomics analysis, the metabolites and targets related to MXFD therapy for migraine were filtered. MXFD was found to alleviate the symptoms of migraines in rats. After treatment with MXFD, nine metabolites were found to be regulated and returned to normal levels. MXFD acted directly on nine key targets including MAOB, MAOA, ADRB1, ADRB2, ADRB3, ADORA2A, ADORA2B, DRD5, and HTR4 and regulated two out of nine metabolites, namely deoxycholic acid and 5-methoxyindoleacetate. The study found that MXFD can alleviate migraines through multitarget and multicomponent interaction networks.

Lycium barbarum polysaccharide reverses drug resistance in oxaliplatin-resistant colon cancer cells by inhibiting PI3K/AKT-dependent phosphomannose isomerase.

Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking. Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50mg/kg), OXA (10mg/kg), or LBP + OXA (50mg/kg + 10mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses. Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5mg/mL LBP, 10μΜ OXA) group (p < 0.05). Cells in the LBP + OXA (2.5mg/mL LBP, 10μΜ OXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 (p < 0.05), while it was found to upregulate Bax (p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumor models showed a decrease in tumor size. There was no difference in the liver index after LBP treatment (p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups (p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels (p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT (p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI. conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC.

Unveiling the mechanism of Buddleja officinalis against esophageal squamous cell carcinoma through network pharmacology and molecular docking approaches

In this research, we aim to explore the underlying mechanism of Buddleja officinalis (BO) in inhibiting esophageal squamous cell carcinoma (ESCC) by means of network pharmacology and molecular docking approaches. First, BO component targets were determined from the Traditional Chinese Medicine Systematic Pharmacology and HERB databases (known as BenCaoZuJian in Chinese transliteration), and ESCC disease targets were identified from GeneCards and DisGeNET databases. Second, the Venny 2.1 online tool was utilized to visualize the intersection targets, and shared potential targets between BO and ESCC were identified using the STRING database. Third, the component-target-pathway networks were constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were utilized for further analyzing the mechanism of BO in inhibiting ESCC. Finally, molecular docking technique was employed to delineate the docking profiles of BO and determine the optimal active component, which is threonine protein kinase (AKT1). We screened six active components and 227 targets from BO, of which 24 were shared targets of ESCC and BO. The network pharmacology analysis indicated core targets with high degrees, namely, serum albumin, insulin-like growth factor 1 receptor, AKT1, estrogen receptor, and basic fibroblast growth factor receptor 1, which are the most likely binding sites for the active components in BO. The related signaling pathways underpinning the inhibition of ESCC by BO encompass MAPK signaling pathway, adhesion junction pathway, and gastric cancer pathway. Moreover, linarin was recognized as the most suitable component for AKT1. Our results revealed that BO exhibits multicomponent, multi-target, and multi-pathway characteristics, which offer a scientific foundation for elucidating its therapeutic mechanism in ESCC and present novel insights for future investigations.

Retracted: Identifying the Effect of Nuanxin Capsules on Myocardial Injury Induced by Chronic Hypoxia via Network Pharmacology Analysis and Experimental Validation.

[This retracts the article DOI: 10.1155/2022/2399462.].