scholarly journals Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qianwen Chen ◽  
Yuanyuan Wang ◽  
Feixiang Ma ◽  
Mengdi Han ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Chain Reaction ◽  
The Common ◽  
Polymerase Chain ◽  
Omim Database

AbstractScabiosa comosa and S. tschilliensis (SCST) are traditionally used for liver diseases in Mongolian medicine. However, their active ingredients and molecular mechanisms are unknown. The present study employed network pharmacology and experimental verification approaches to decipher the common pharmacological mechanisms of SCST on liver fibrosis, which is the key step in liver diseases. We predicted the targets of all available SCST ingredients with the SWISS and SuperPred servers and clustered the targets related to liver fibrosis from DrugBank, the OMIM database and the literature. We further evaluated the links between the herbal ingredients and pharmacological actions to explore the potential mechanism of action of SCST. We found that the PPARG signalling pathway could be regulated by SCST for liver fibrosis through enrichment analysis. The key targets included 8 co-targets, including HSP90AA1, PPARG, HSP90AB1, STAT1, etc., which play pivotal roles in the pathogenesis of liver fibrosis. Additionally, the top 15 key compounds included flavonoids and phenylpropanoids. Central to the pathogenesis of liver fibrosis is trans-differentiation or activation of hepatic stellate cells (HSCs). Therefore, LX2 cells, an immortalized human HSC line, were studied. Here, a total 37 components were isolated and identified from the inflorescences of SCST, including the new compound tschilliensisin, and the first separated components, β-sitosterol and luteolin, and these compounds were assessed against anti-hepatic fibrosis. An MTT assay and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses demonstrated that the flavonoids of SCST revealed anti-hepatic fibrosis effects via anti-proliferation and increases in the Stat1, Pparg, Hsp90aa1 genes and STAT1 and PPARG proteins in LX-2 cells. In conclusion, these results indicate that SCST has multi-targeted and multi-component synergistic anti-hepatic fibrosis effects.

scholarly journals The Potential Application of Magnetic Nanoparticles for Liver Fibrosis Theranostics

2021 ◽  
Vol 9 ◽  
Author(s):  
Aziz Eftekhari ◽  
Allahveirdy Arjmand ◽  
Ayyub Asheghvatan ◽  
Helena Švajdlenková ◽  
Ondrej Šauša ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Tissue Penetration ◽  
Specific Therapy ◽  
Chronic Liver Damage ◽  
Superparamagnetic Properties ◽  
New Strategies

Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic liver damage and leading to cirrhosis, liver cancer, and liver failure. To date, there is no effective and specific therapy for patients with hepatic fibrosis. As a result of their various advantages such as biocompatibility, imaging contrast ability, improved tissue penetration, and superparamagnetic properties, magnetic nanoparticles have a great potential for diagnosis and therapy in various liver diseases including fibrosis. In this review, we focus on the molecular mechanisms and important factors for hepatic fibrosis and on potential magnetic nanoparticles-based therapeutics. New strategies for the diagnosis of liver fibrosis are also discussed, with a summary of the challenges and perspectives in the translational application of magnetic nanoparticles from bench to bedside.

HEPATIC FIBROSIS: Molecular Mechanisms and Drug Targets

2005 ◽  
Vol 45 (1) ◽  
pp. 605-628 ◽  
Author(s):  
Sophie Lotersztajn ◽  
Boris Julien ◽  
Fatima Teixeira-Clerc ◽  
Pascale Grenard ◽  
Ariane Mallat
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Current Treatment ◽  
Culture Studies ◽  
Common Response ◽  
The Common ◽  
Parenchymal Injury ◽  
Antifibrotic Drugs

Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis and its complications, portal hypertension, liver failure, and hepatocellular carcinoma. Efficient and well-tolerated antifibrotic drugs are currently lacking, and current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Efforts over the past decade have mainly focused on fibrogenic cells generating the scarring response, although promising data on inhibition of parenchymal injury and/or reduction of liver inflammation have also been obtained. A large number of approaches have been validated in culture studies and in animal models, and several clinical trials are underway or anticipated for a growing number of molecules. This review highlights recent advances in the molecular mechanisms of liver fibrosis and discusses mechanistically based strategies that have recently emerged.

scholarly journals Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Biting Wang ◽  
Zengrui Wu ◽  
Weihua Li ◽  
Guixia Liu ◽  
Yun Tang
Keyword(s):  
Molecular Docking ◽  
Liver Fibrosis ◽  
Molecular Mechanisms ◽  
Docking Simulation ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Bipartite Network ◽  
Metabolomics Data ◽  
Metabolic Products ◽  
Compound Target

Abstract Background The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods. Methods Firstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein–protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed. Results 68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway. Conclusions This study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.

scholarly journals Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mingxu Zhang ◽  
Jiawei Yang ◽  
Xiulan Zhao ◽  
Ying Zhao ◽  
Siquan Zhu
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Enrichment Analysis ◽  
Docking Study ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Ingredients ◽  
Molecular Docking Study

AbstractDiabetic retinopathy (DR) is a leading cause of irreversible blindness globally. Qidengmingmu Capsule (QC) is a Chinese patent medicine used to treat DR, but the molecular mechanism of the treatment remains unknown. In this study, we identified and validated potential molecular mechanisms involved in the treatment of DR with QC via network pharmacology and molecular docking methods. The results of Ingredient-DR Target Network showed that 134 common targets and 20 active ingredients of QC were involved. According to the results of enrichment analysis, 2307 biological processes and 40 pathways were related to the treatment effects. Most of these processes and pathways were important for cell survival and were associated with many key factors in DR, such as vascular endothelial growth factor-A (VEGFA), hypoxia-inducible factor-1A (HIF-1Α), and tumor necrosis factor-α (TNFα). Based on the results of the PPI network and KEGG enrichment analyses, we selected AKT1, HIF-1α, VEGFA, TNFα and their corresponding active ingredients for molecular docking. According to the molecular docking results, several key targets of DR (including AKT1, HIF-1α, VEGFA, and TNFα) can form stable bonds with the corresponding active ingredients of QC. In conclusion, through network pharmacology methods, we found that potential biological mechanisms involved in the alleviation of DR by QC are related to multiple biological processes and signaling pathways. The molecular docking results also provide us with sound directions for further experiments.

scholarly journals The roles and mechanisms of hypoxia in liver fibrosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyao Cai ◽  
Min Hu ◽  
Zhiyang Chen ◽  
Zeng Ling
Keyword(s):  
Quality Of Life ◽  
Liver Fibrosis ◽  
Theoretical Basis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Clinical Intervention ◽  
Chronic Liver Injury ◽  
Key Factor

AbstractLiver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.

scholarly journals Placental Cytomegalovirus Infection

2018 ◽  
Vol 143 (5) ◽  
pp. 639-642 ◽  
Author(s):  
Kaleigh Lindholm ◽  
Mary O'Keefe
Keyword(s):  
The United States ◽  
Late Sequelae ◽  
Chain Reaction ◽  
Fetal Demise ◽  
Live Births ◽  
Delayed Onset ◽  
Viral Culture ◽  
Intracytoplasmic Inclusions ◽  
The Common ◽  
Polymerase Chain

In the United States, cytomegalovirus is the most common congenital viral infection and the number 1 cause of nonhereditary sensorineural hearing loss. The vast majority of infants may be asymptomatic, especially if cytomegalovirus is contracted later in the pregnancy, and some symptoms may have a delayed onset. Therefore, it is important for the pathologist to identify the common histologic findings to help confirm the diagnosis so the child can be followed for late sequelae. Histologic examination of the placenta is important in live births and in cases of intrauterine fetal demise. Chronic lymphoplasmacytic villitis and fibrotic, avascular villi are the most common findings. When present, Cowdry A intranuclear and basophilic intracytoplasmic inclusions are characteristic. Immunohistochemistry for cytomegalovirus can highlight these inclusions as well as the associated eosinophilic debris. In addition, polymerase chain reaction or viral culture on placental or fetal samples can be performed for confirmation.

scholarly journals Elucidation of the mechanisms and molecular targets of Qishen Yiqi formula for the treatment of pulmonary arterial hypertension using a bioinformatics/network topology-based strategy

2020 ◽  
Vol 23 ◽  
Author(s):  
Peiliang Wu ◽  
Xiaona Xie ◽  
Mayun Chen ◽  
Junwei Sun ◽  
Luqiong Cai ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Network Topology ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Bioactive Ingredients ◽  
Pulmonary Arterial

Background and Objective: Qishen Yiqi formula (QSYQ) is used to treat cardiovascular disease in the clinical practice of traditional Chinese medicine. However, few studies have explored whether QSYQ affects pulmonary arterial hypertension (PAH), and the mechanisms of action and molecular targets of QSYQ for the treatment of PAH are unclear. A bioinformatics/network topology-based strategy was used to identify the bioactive ingredients, putative targets, and molecular mechanisms of QSYQ in PAH. Methods: A network pharmacology-based strategy was employed by integrating active component gathering, target prediction, PAH gene collection, network topology, and gene enrichment analysis to systematically explore the multicomponent synergistic mechanisms. Results: In total, 107 bioactive ingredients of QSYQ and 228 ingredient targets were identified. Moreover, 234 PAH-related differentially expressed genes with a |fold change| >2 and an adjusted P value < 0.005 were identified between the PAH patient and control groups, and 266 therapeutic targets were identified. The pathway enrichment analysis indicated that 85 pathways, including the PI3K-Akt, MAPK, and HIF-1 signaling pathways, were significantly enriched. TP53 was the core target gene, and 7 other top genes (MAPK1, RELA, NFKB1, CDKN1A, AKT1, MYC, and MDM2) were the key genes in the gene-pathway network based on the effects of QSYQ on PAH. Conclusion: An integrative investigation based on network pharmacology may elucidate the multicomponent synergistic mechanisms of QSYQ in PAH and lay a foundation for further animal experiments, human clinical trials and rational clinical applications of QSYQ.

scholarly journals Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi Zhu ◽  
Ming Qiao ◽  
Jianhua Yang ◽  
Junping Hu
Keyword(s):  
Liver Fibrosis ◽  
Rna Polymerase Ii ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Docking Simulation ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Transcription Activator ◽  
Active Ingredients ◽  
Oxidoreductase Activity

Objective. To holistically explore the latent active ingredients, targets, and related mechanisms of Hugan buzure granule (HBG) in the treatment of liver fibrosis (LF) via network pharmacology. Methods. First, we collected the ingredients of HBG by referring the TCMSP server and literature and filtered the active ingredients though the criteria of oral bioavailability ≥30% and drug-likeness index ≥0.18. Second, herb-associated targets were predicted and screened based on the BATMAN-TCM and SwissTargetPrediction platforms. Candidate targets related to LF were collected from the GeneCards and OMIM databases. Furthermore, the overlapping target genes were used to construct the protein-protein interaction network and “drug-compound-target-disease” network. Third, GO and KEGG pathway analyses were carried out to illustrate the latent mechanisms of HBG in the treatment of LF. Finally, the combining activities of hub targets with active ingredients were further verified based on software AutoDock Vina. Results. A total of 25 active ingredients and 115 overlapping target genes of HBG and LF were collected. Besides, GO enrichment analysis exhibited that the overlapping target genes were involved in DNA-binding transcription activator activity, RNA polymerase II-specific, and oxidoreductase activity. Simultaneously, the key molecular mechanisms of HBG against LF were mainly involved in PI3K-AKT, MAPK, HIF-1, and NF-κB signaling pathways. Also, molecular docking simulation demonstrated that the key targets of HBG for antiliver fibrosis were IL6, CASP3, EGFR, VEGF, and MAPK. Conclusion. This work validated and predicted the underlying mechanisms of multicomponent and multitarget about HBG in treating LF and provided a scientific foundation for further research.

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