scholarly journals Identifying Active Compounds and Mechanism of Camellia nitidissima Chi on Anti-Colon Cancer by Network Pharmacology and Experimental Validation

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yiwei Chen ◽  
Erwei Hao ◽  
Fan Zhang ◽  
Zhengcai Du ◽  
Jinling Xie ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Experimental Validation ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cell Model ◽  
Hct116 Cell ◽  
Network Pharmacology ◽  
Kegg Analysis ◽  
Camellia Nitidissima

Camellia nitidissima Chi (CNC) is a traditional Chinese medicine (TCM) with anticancer property. However, its underlying mechanisms of anti-colon cancer (CC) remain unknown. Therefore, a systematic approach is proposed in the present study to elucidate the anticancer mechanisms of CNC based on network pharmacology and experimental validation. Initially, the potential active ingredients of CNC were verified via the TCMSP database based on the oral bioavailability (OB) and drug-likeness (DL) terms. Hub targets of CNC were acquired from SwissTarget prediction and TCMSP databases, and target genes related to CC were gathered from GeneCards and OMIM databases. Cytoscape was used to establish the compound-target networks. Next, the hub target genes collected from the CNC and CC were parsed via GO and KEGG analysis. Results of GO and KEGG analysis reveal that quercetin and luteolin in CNC, VEGFA and AKT1 targets, and PI3K-Akt pathway were associated with the suppression of CC. Besides, the result of molecular docking unveils that VEGFA demonstrates the most powerful binding affinity among the binding outcomes. This finding was successfully validated using in vitro HCT116 cell model experiment. In conclusion, this study proved the usefulness of integrating network pharmacology with in vitro experiments in the elucidation of underlying molecular mechanisms of TCM.

scholarly journals Identification of the Active Constituents and Significant Pathways of Shen-qi-Yi-zhu Decoction on Antigastric Cancer: A Network Pharmacology Research and Experimental Validation

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shuhong Zeng ◽  
Zhibao Yu ◽  
Xintian Xu ◽  
Yuanjie Liu ◽  
Jiepin Li ◽  
...  
Keyword(s):  
Experimental Validation ◽  
Target Genes ◽  
Cell Model ◽  
Network Pharmacology ◽  
Disease Network ◽  
Systematic Method ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Underlying Mechanisms

Shen-qi-Yi-zhu decoction (SQYZD) is an empirical prescription with antigastric cancer (GC) property created by Xu Jing-fan, a National Chinese Medical Master. However, its underlying mechanisms are still unclear. Based on network pharmacology and experimental verification, this study puts forward a systematic method to clarify the anti-GC mechanism of SQYZD. The active ingredients of SQYZD and their potential targets were acquired from the TCMSP database. The target genes related to GC gathered from GeneCards, DisGeNET, OMIM, TTD, and DrugBank databases were imported to establish protein-protein interaction (PPI) networks in GeneMANIA. Cytoscape was used to establish the drug-ingredients-targets-disease network. The hub target genes collected from the SQYZD and GC were parsed via GO and KEGG analysis. Our findings from network pharmacology were successfully validated using an in vitro HGC27 cell model experiment. In a word, this study proves that the combination of network pharmacology and in vitro experiments is effective in clarifying the potential molecular mechanism of traditional Chinese medicine (TCM).

scholarly journals Prediction of the Molecular Mechanisms Underlying Erlong Zuoci Treatment of Age-Related Hearing Loss via Network Pharmacology-Based Analyses Combined with Experimental Validation

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Liu ◽  
Ning Li ◽  
Yifang Yang ◽  
Xirui Yan ◽  
Yang Dong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Experimental Validation ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Synaptic Connections ◽  
Target Proteins ◽  
Age Related ◽  
Age Related Hearing Loss

Background: The traditional Chinese medicine formula ErLong ZuoCi (ELZC) has been extensively used to treat age-related hearing loss (ARHL) in clinical practice in China for centuries. However, the underlying molecular mechanisms are still poorly understood.Objective: Combine network pharmacology with experimental validation to explore the potential molecular mechanisms underlying ELZC with a systematic viewpoint.Methods: The chemical components of ELZC were collected from the Traditional Chinese Medicine System Pharmacology database, and their possible target proteins were predicted using the SwissTargetPrediction database. The putative ARHL-related target proteins were identified from the database: GeneCards and OMIM. We constructed the drug-target network as well as drug-disease specific protein-protein interaction networks and performed clustering and topological property analyses. Functional annotation and signaling pathways were performed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Finally, in vitro experiments were also performed to validate ELZC’s key target proteins and treatment effects on ARHL.Results: In total, 63 chemical compounds from ELZC and 365 putative ARHL-related targets were identified, and 1860 ARHL-related targets were collected from the OMIM and GeneCards. A total of 145 shared targets of ELZC and ARHL were acquired by Venn diagram analysis. Functional enrichment analysis suggested that ELZC might exert its pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and the potential targets might be associated with AKT, ERK, and STAT3, as well as other proteins. In vitro experiments revealed that ELZC pretreatment could decrease senescence-associated β-galactosidase activity in hydrogen peroxide-induced auditory hair cells, eliminate DNA damage, and reduce cellular senescence protein p21 and p53. Finally, Western blot analysis confirmed that ELZC could upregulate the predicted target ERK phosphorylation.Conclusion: We provide an integrative network pharmacology approach, in combination with in vitro experiments to explore the underlying molecular mechanisms governing ELZC treatment of ARHL. The protective effects of ELZC against ARHL were predicted to be associated with cellular senescence, inflammatory response, and synaptic connections which might be linked to various pathways such as JNK/STAT3 and ERK cascade signaling pathways. As a prosperous possibility, our experimental data suggest phosphorylation ERK is essential for ELZC to prevent degeneration of cochlear.

scholarly journals Identification on the potential mechanism of Radix pueraria on colon cancer based on network pharmacology

2021 ◽  
Author(s):  
Yi Li ◽  
Chunli Zhang ◽  
Xiaohan Ma ◽  
Liuqing Yang ◽  
Huijun Ren
Keyword(s):  
Colon Cancer ◽  
Chinese Medicine ◽  
Target Genes ◽  
Enrichment Analysis ◽  
In Vivo Studies ◽  
Network Pharmacology ◽  
Biological Mechanism ◽  
Active Components

Abstract Radix Puerariae (RP), a dry root of the Pueraria lobata (Willd.) Ohwi, is used to treat a variety of diseases, including cancer. Several in vitro and in vivo studies have demonstrated the efficacy of RP in the treatment of colon cancer (CC). However, the biological mechanism of RP in the treatment of colon cancer remains unclear. In this study, the active component of RP and its potential molecular mechanism against CC were studied by network pharmacology and enrichment analysis. The methods adopted included screening of active ingredients of Chinese medicine, prediction of target genes of Chinese medicine and disease, construction of protein interaction network, and GO and KEGG Enrichment Analysis. Finally, the results of network pharmacology were further validated by molecular docking experiments and cell experiments. 8 active constituents and 14 potential protein targets were screened from RP, including EGFR, JAK2 and SRC. The biological mechanism of RP against CC was analyzed by studying the relationship between active components, targets, and enrichment pathway. This provides a basis for understanding the clinical application of RP in CC.

scholarly journals Network pharmacology based virtual screening of active constituents of Prunella vulgaris L. and the molecular mechanism against breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaobo Zhang ◽  
Tao Shen ◽  
Xin Zhou ◽  
Xuehua Tang ◽  
Rui Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Perennial Herb ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Prunella Vulgaris ◽  
Biological Mechanisms ◽  
Active Constituents

Abstract Prunella vulgaris L, a perennial herb widely used in Asia in the treatment of various diseases including cancer. In vitro studies have demonstrated the therapeutic effect of Prunella vulgaris L. against breast cancer through multiple pathways. However, the nature of the biological mechanisms remains unclear. In this study, a Network pharmacology based approach was used to explore active constituents and potential molecular mechanisms of Prunella vulgaris L. for the treatment of breast cancer. The methods adopted included active constituents prescreening, target prediction, GO and KEGG pathway enrichment analysis. Molecular docking experiments were used to further validate network pharmacology results. The predicted results showed that there were 19 active ingredients in Prunella vulgaris L. and 31 potential gene targets including AKT1, EGFR, MYC, and VEGFA. Further, analysis of the potential biological mechanisms of Prunella vulgaris L. against breast cancer was performed by investigating the relationship between the active constituents, target genes and pathways. Network analysis showed that Prunella vulgaris L. exerted a promising preventive effect on breast cancer by acting on tumor-associated signaling pathways. This provides a basis to understand the mechanism of the anti-breast cancer activity of Prunella vulgaris L.

scholarly journals The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 453
Author(s):  
Susana M. Chuva de Sousa Lopes ◽  
Marta S. Alexdottir ◽  
Gudrun Valdimarsdottir
Keyword(s):  
Stem Cell ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cell Model ◽  
Embryonic Stem ◽  
Model Systems ◽  
Special Focus ◽  
Placental Development

Emerging data suggest that a trophoblast stem cell (TSC) population exists in the early human placenta. However, in vitro stem cell culture models are still in development and it remains under debate how well they reflect primary trophoblast (TB) cells. The absence of robust protocols to generate TSCs from humans has resulted in limited knowledge of the molecular mechanisms that regulate human placental development and TB lineage specification when compared to other human embryonic stem cells (hESCs). As placentation in mouse and human differ considerably, it is only with the development of human-based disease models using TSCs that we will be able to understand the various diseases caused by abnormal placentation in humans, such as preeclampsia. In this review, we summarize the knowledge on normal human placental development, the placental disease preeclampsia, and current stem cell model systems used to mimic TB differentiation. A special focus is given to the transforming growth factor-beta (TGFβ) family as it has been shown that the TGFβ family has an important role in human placental development and disease.

7-hydroxyfrullanolide, isolated from Sphaeranthus indicus, inhibits colorectal cancer cell growth by p53-dependent and -independent mechanism

2018 ◽  
Vol 40 (6) ◽  
pp. 791-804
Author(s):  
Praveen Pandey ◽  
Deepika Singh ◽  
Mohammad Hasanain ◽  
Raghib Ashraf ◽  
Mayank Maheshwari ◽  
...  
Keyword(s):  
Cell Growth ◽  
Anticancer Activity ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cancer Cell Growth ◽  
Apoptotic Pathway ◽  
Syngeneic Mouse Model ◽  
Sphaeranthus Indicus

Abstract Sphaeranthus indicus Linn. is commonly used in Indian traditional medicine for management of multiple pathological conditions. However, there are limited studies on anticancer activity of this plant and its underlying molecular mechanisms. Here, we isolated an active constituent, 7-hydroxyfrullanolide (7-HF), from the flowers of this plant, which showed promising chemotherapeutic potential. The compound was more effective in inhibiting in vitro proliferation of colon cancers cells through G2/M phase arrest than other cancer cell lines that were used in this study. Consistent with in vitro data, 7-HF caused substantial regression of tumour volume in a syngeneic mouse model of colon cancer. The molecule triggered extrinsic apoptotic pathway, which was evident as upregulation of DR4 and DR5 expression as well as induction of their downstream effector molecules (FADD, Caspase-8). Concurrent activation of intrinsic pathway was demonstrated with loss of ΔΨm to release pro-apoptotic cytochrome c from mitochondria and activation of downstream caspase cascades (Caspase -9, -3). Loss of p53 resulted in decreased sensitivity of cells towards pro-apoptotic effect of 7-HF with increased number of viable cells indicating p53-dependent arrest of cancer cell growth. This notion was further supported with 7-HF-mediated elevation of endogenous p53 level, decreased expression of MDM2 and transcriptional upregulation of p53 target genes in apoptotic pathway. However, 7-HF was equally effective in preventing progression of HCT116 p53+/+ and p53−/− cell derived xenografts in nude mice, which suggests that differences in p53 status may not influence its in vivo efficacy. Taken together, our results support 7-HF as a potential chemotherapeutic agent and provided a new mechanistic insight into its anticancer activity.

scholarly journals A Network Pharmacology Approach to Predict the Proangiogenesis Mechanism of Huangqi-Honghua Herb Pair after Cerebral Ischemia

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jinyi Cao ◽  
Lu Lei ◽  
Kai Wang ◽  
Jing Sun ◽  
Yi Qiao ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Blood Stasis ◽  
Blood Stasis Syndrome ◽  
Network Pharmacology ◽  
Western Blot Assay ◽  
Medicinal Value ◽  
Pharmacological Method

Objective. Huangqi-Honghua herb pair is known for its medicinal value to treat Qi deficiency and blood stasis syndrome with a long history in clinical practice. To understand its possible mechanism in a systematic study, a network pharmacological method was addressed. Methods. Detailed information on the HH compounds was obtained from two public databases, and oral bioavailability (OB) and drug-like (DL) of the compounds were evaluated. A correlation between HH compounds, its potential targets, and known targets was extrapolated, and the herb-compound-target-disease (H-C-T-D) network was established. Next, the pathway enrichment and essential genes were analyzed. Then, three key genes (VEGFA, VEGFR2, and eNOS), highly associated with angiogenesis, were screened and verified through western blot assay. Results. Out of 276 compounds, 21 HH compounds and 78 target genes regulating the major pathways associated with CI in the network are analyzed. The bioactive compounds in HH were active in various signal transduction pathways such as the toll-like receptor signaling pathway, VEGF signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway are important pathways that may regulate anti-inflammatory, antiapoptotic, immune correlation, and antioxidative effects. The core genes are PTGS2, TNF, NOS2, IL6, BCL2, IL1B, SOD2, NOS3, SOD1, MMP9, and VEGFA. The in vitro results suggested that HH treatment could significantly elevate the expression of proangiogenic genes such as VEGFA, VEGFR2, and eNOS compared with OGD groups. Conclusions. Our results predict that HH may regulate the expression of VEGFA, VEGFR2, and eNOS via the VEGF and HIF-1 signaling pathway to promote angiogenesis and alleviate cerebral ischemia injury.

scholarly journals Bioinformatic and experimental findings to indicate anti-cancer targets and mechanisms of calycosin against nasopharyngeal carcinoma

2020 ◽  
Author(s):  
Fangxian Liu ◽  
Qijin Pan ◽  
Liangliang Wang ◽  
Shijiang Yi ◽  
Peng Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cell Number ◽  
Network Pharmacology ◽  
Tunel Staining ◽  
Pharmacological Targets ◽  
Experimental Findings

Abstract Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.

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.

Schisandrin B Attenuates Colitis-Associated Colorectal Cancer through SIRT1 Linked SMURF2 Signaling

2021 ◽  
pp. 1-17
Author(s):  
Zhichen Pu ◽  
Weiwei Zhang ◽  
Minhui Wang ◽  
Maodi Xu ◽  
Haitang Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Growth ◽  
Protein Expression ◽  
Hct116 Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Schisandrin B ◽  
In Vivo Models

Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75–30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 in vitro and in vivo. SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both in vitro and in vivo models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.

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