Curcumin mediates autophagy and apoptosis in granulosa cells: a study of integrated network pharmacology and molecular docking to elucidate toxicological mechanisms

Venenum Bufonis (VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components–main HF putative targets–main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM.

Download Full-text

Peer Review #2 of "Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in Venenum Bufonis for ameliorating heart failure (v0.1)"

10.7287/peerj.10107v0.1/reviews/2 ◽

2020 ◽

Keyword(s):

Heart Failure ◽

Molecular Docking ◽

Peer Review ◽

Network Pharmacology ◽

Integrated Network ◽

Multiple Components ◽

Synergistic Mechanism

Download Full-text

Therapeutic Potential of Curcumin on the Cognitive Decline in Alzheimer’s Disease: A Study Integrated Meta-Analysis, Network Pharmacology, and Molecular Docking

10.21203/rs.3.rs-590600/v1 ◽

2021 ◽

Author(s):

Zheyu Zhang ◽

Hongli Li ◽

Shan Hui ◽

Min Yi ◽

Xin Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Cognitive Deficits ◽

Therapeutic Potential ◽

Meta Analysis ◽

Scientific Basis ◽

Network Pharmacology ◽

Integrated Network ◽

Positive Effects

Abstract Background: Curcumin, a polyphenol derived from the herb turmeric, has emerged as a promising potential therapy in the management of Alzheimer’s disease (AD). However, the efficacy and potential therapeutic mechanisms remains largely unknown. Objective: To systematically meta-analysis the eﬀect and to investigate the potential pharmacological mechanisms of curcumin on cognitive deficits in AD. Methods: A systematic collection of curcumin studies was performed from MEDLINE’s database, PubMed, Web of Science, and Google Scholar until October 31th, 2020. Following quality assessment of study eligibility, stratified meta-analysis and meta-regression analyses were undertaken to recognize and control the heterogeneity in meta-analysis. An integrated network pharmacology and molecular docking approach were applied to decipher the potential pharmacological mechanisms of curcumin on AD. Results: A meta-analysis of 29 publications showed that curcumin exerts significantly positive eﬀects on cognitive performance. For acquisition, the global estimated effect of curcumin was -2.027 (95% CI: -2.435 to -1.619, p<0.001); For retention, the global estimated effect of curcumin was 1.606 (95% CI: 1.101 to 2.111, p<0.001). Stratified meta-analysis demonstrated that an increased effect size depended on various study characteristics. Network pharmacology analysis identified 63 genes targets, and STAT3, CHEK1, AKT1, EGFR, MMP9, hsp90AA1, and EP300 were core target proteins. Molecular docking showed that curcumin can closely bind with these seven targets. Besides, 69 potential pathways of curcumin were identified, like nitrogen metabolism.Conclusions: Our findings suggested that curcumin may reduce cognitive deficits in AD through multi-target and multi-pathway mechanism, providing a scientific basis for further experimental and clinical application.

Download Full-text

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

10.21203/rs.3.rs-38111/v2 ◽

2020 ◽

Author(s):

MengMeng Zhang ◽

Dan Wang ◽

Feng Lu ◽

Rong Zhao ◽

Xun Ye ◽

...

Keyword(s):

Colon Cancer ◽

Molecular Docking ◽

Cancer Prevention ◽

Signaling Pathways ◽

Cellular Response ◽

Endocrine Resistance ◽

Docking Simulation ◽

Network Pharmacology ◽

Integrated Network ◽

Colon Cancer Prevention

Abstract Background and objective: Colon cancer is increasing in people recently and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent against colon cancer. This study was aimed to identify the bioactive compounds and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach.Methods: Putative ingredients of ginger and its related targets were discerned from the TCMSP database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape.Results: Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, including cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, MAPK8, JAK2, CASP3, and ERBB2 were viewed as the most important genes, which were validated by molecular docking simulation.Conclusion: This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-target and multi-pathway with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.

Download Full-text

Peer Review #3 of "Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in Venenum Bufonis for ameliorating heart failure (v0.1)"

10.7287/peerj.10107v0.1/reviews/3 ◽

2020 ◽

Keyword(s):

Heart Failure ◽

Molecular Docking ◽

Peer Review ◽

Network Pharmacology ◽

Integrated Network ◽

Multiple Components ◽

Synergistic Mechanism

Download Full-text

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

Chinese Medicine ◽

10.1186/s13020-021-00473-8 ◽

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.

Download Full-text