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

Project description:BackgroundThis study employs network pharmacology and molecular docking methods in conjunction with animal experimentation to elucidate the underlying mechanism by which the combination of salvianolic phenolic acids and hawthorn triterpenic acids (SHC) exerts its therapeutic effect on carotid atherosclerosis (AS) in ApoE-/- mice.MethodsA network pharmacology research approach was used to predict potential core targets for SHC intervention in atherosclerosis. The predictions were subsequently validated through the implementation of animal in vivo experiments. ApoE-/- mice were randomly assigned to three experimental groups, namely, a model group, an atorvastatin group, and an SHC group. After the administration period, the plaque area in the carotid artery and aortic arch, blood lipid levels, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and nitric oxide (NO) content were measured. Additionally, the expression of PI3K, Akt, NF-κB, JNK1, ERK1/2, and p38-MAPK in the aortic arteries was analyzed. Based on the protein expression results, molecular docking was used to predict the binding activity between the core compounds and core targets.ResultsA total of 23 core compounds were identified in SHC, and 55 core targets of SHC were screened as potential targets for intervention in AS. The results of the enrichment analysis indicated that the principal mechanisms through which SHC exerts its effects in AS are associated with lipid metabolism and the PI3K-Akt and MAPK pathways. The results from animal experiments demonstrated that atorvastatin and SHC markedly reduced the area of carotid plaque and downregulated the levels of TC and LDL-C in ApoE-/- mice. The administration of SHC was associated with an increase in SOD activity and a reduction in NO levels in the livers of mice. Furthermore, SHC was observed to downregulate the expression of NF-κB and p38-MAPK in the carotid region. The results of molecular docking demonstrated that the core compounds of SHC, including salvianolic acid A, B, and C, maslinic acid, ursolic acid, and oleic acid, were capable of stably binding to the core targets NF-κB and MAPK14.ConclusionIt is hypothesized that SHC may reduce lipid deposition and plaque formation in AS by regulating blood lipids, a process that may be closely linked to the inhibition of inflammatory regulator expression, including NF-κB and p38-MAPK.

Project description:The BixizelanYin (BXZLY) is a traditional herbal formula for treating damp-heat type knee osteoarthritis (KOA). This study aimed to investigate the potential therapeutic effects of BXZLY on KOA by using network pharmacology and molecular docking. Active ingredients and their corresponding targets of BXZLY were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The known disease targets of KOA were retrieved from GeneCards and the Online Mendelian Inheritance in Man database. The effective targets of BXZLY for treating KOA were obtained with the Venny platform. A drug-component-target network diagram was constructed using Cytoscape 3.7.2 software, and a protein-protein interaction network was established via the STRING database. The protein-protein interaction network was visualized by Cytoscape 3.7.2 software. The biological functions of the targets wereanalyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis with the DAVID database. The Gene Ontology enrichment and KEGG pathway visualization bubble charts were generated using the OmicShare online platform to explore the biological functions of BXZLY in treating KOA. The main signaling pathways of BXZLY in treating KOA were investigated by KEGG pathway enrichment analysis. Finally, AutoDockTools software was used for molecular docking validation of the key molecules of the drug and the key proteins of the disease. A total of 108 active compounds and 280 target proteins of BXZLY were identified. There were 2816 disease-related targets related to KOA, among which 99 were targeted by BXZLY for KOA treatment. Key compounds included β-sitosterol, stigmasterol, campesterol, quercetin, and dioscin. Core target proteins consisted of STAT3, ESR1, EGFR, JUN, and PTGS2. The pathways mainly involved the advanced glycation end products - receptor for advanced glycation end products, estrogen, HIF-1, and relaxin signal pathways. Molecular docking showed a strong binding affinity between active ingredients and core target proteins. Docking candidates were selected based on oral bioavailability ≥ 30%, drug-likeness ≥ 0.18, and degree values in Cytoscape. This strategy ensured a reliable selection of compounds with high therapeutic relevance. BXZLY provides a comprehensive therapeutic strategy for KOA treatment by regulating cell proliferation and alleviating inflammation through its multi-component, multi-target, and multi-pathway effects.

Project description:BackgroundCurrent prostate cancer treatments are associated with life-threatening side effects, prompting the search for effective and safer alternatives. Aspilia pluriseta Schweinf. ex Engl. has previously shown anticancer activity in lung and liver cancer cell lines. This study investigated its potential for prostate cancer.MethodsA crude extract of A. pluriseta root was prepared using dichloromethane/methanol (1:1 v/v) and partitioned into hexane, ethyl acetate, and water fractions. The MTT assay was used to assess the antiproliferative activity of the fractions. The active fractions were tested at 6.25-200 µg/ml on human prostate cancer DU-145 cells and non-cancerous Vero E6 cells. Qualitative phytochemical and gas chromatography-mass spectrometry (GC-MS) analyses were conducted to identify chemical compounds. Network pharmacology was employed to predict molecular targets and modes of action of the identified chemical compounds, with subsequent validation through molecular docking and real-time PCR.ResultsActive extracts included crude dichloromethane/methanol, hexane, and ethyl acetate fractions, inhibiting DU-145 cell proliferation with IC50 values of 16.94, 20.06, and 24.14 µg/ml, respectively. Selectivity indices were determined to be 6.04 (crude), 3.62 (hexane), and 6.68 (ethyl acetate). Identified phytochemicals comprised phenols, terpenoids, flavonoids, tannins, sterols, and saponins. GC-MS analysis revealed seventy-nine (79) compounds, with seven (7) meeting ideal drug candidate parameters; their hub gene targets included MAPK3, MAPK1, IL6, TP53, ESR1, PTGS2, MMP9, MDM2, AR, and MAP2K1, implicating regulation of PI3K/Akt, MAPK, and p53 signaling pathways as potential modes of action. Core compounds such as 1-heneicosanol, lanosterol, andrographolide, and retinoic acid exhibited strong binding activities, particularly lanosterol with MAPK21 (-9.7 kcal/mol), ESR1 (-8.9 kcal/mol), and MAPK3 (-8.8 kcal/mol). Treatment with A. pluriseta downregulated AR expression and upregulated p53, while also downregulating CDK1 and BCL-2 and upregulating caspase-3.ConclusionsA. pluriseta extracts inhibited DU-145 cell growth without causing cellular toxicity, suggesting great potential for development as an anti-prostate cancer agent. However, further in vitro and in vivo experiments are recommended.

Project description:Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.

Project description:ObjectiveYikunyin is an empirical prescription that exhibits good efficacy in the clinical treatment of menopausal syndrome; however, its underlying mechanism remains unclear. This study investigates the mechanism implicated in the therapeutic effect of Yikunyin by identifying its hub genes, central pathways, and key active ingredients.MethodThe active ingredients and targets of Yikunyin were obtained from the Traditional Chinese Medicine Systems Pharmacology database, whereas the targets related to menopausal syndrome were obtained from GeneCards, PharmGKB, Therapeutic Target Database (TTD), and Comparative Toxicogenomics Database (CTD). To reveal the pharmacological mechanism, the component-target and the intersecting protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Finally, molecular docking was carried out to assess the strength of binding between the key active ingredients and key targets.ResultsA total of 418 targets and 121 active ingredients were identified in Yikunyin. The intersection of Yikunyin's 418 targets with the 2822 targets related to menopausal syndrome shows that there are 247 common targets that can be considered potential targets of Yikunyin in the treatment of menopausal syndrome. The topology analysis of the constructed PPI network conducted using the Cytoscape software shows that there are 15 hub genes implicated in the therapeutic effect of Yikunyin: AKT1, PRKCA, TLR9, CXCL10, PRKCD, PARP1, ABCB1, TP53, CAV1, MAPK8, PPARA, GRB2, EGFR, IL-6, and JAK2. Moreover, the key active components acting on these genes are paeoniflorin, luteolin, quercetin, beta-sitosterol, and kaempferol. GO and KEGG analyses indicate that Yikunyin can treat menopausal syndrome by regulating cellular response to chemical stress (GO:0062197), cellular response to oxidative stress (GO:0034599), phosphatase binding (GO:0019902), cytokine receptor binding (GO:0005126), PI3K-Akt signaling (hsa04151), lipid and atherosclerosis (hsa05417), and hepatitis B (hsa05161). Finally, the results of molecular docking suggest that the key active ingredients and key targets can bind well, with binding energies of less than -5 kJ/mol.ConclusionThe research conducted herein reveals that Yikunyin treats menopausal syndrome by targeting AKT1 and IL-6 and by regulating the PI3K-Akt signaling pathway. Moreover, it provides a new idea for understanding the therapeutic effects of traditional Chinese medicines.

Dataset Information

Effect of Shan Zha (Hawthorn or Crataegus) on gastrointestinal cancer: A network pharmacology and molecular docking study

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets