Exploring the mechanism of aloe-emodin in the treatment of liver cancer through network pharmacology and cell experiments.

Zhu M ，He Q ，Wang Y ，Duan L ，Rong K ，Wu Y ，Ding Y ，Mi Y ，Ge X ，Yang X ，Yu Y ... -  《Frontiers in Pharmacology》

Mechanism of emodin in treating hepatitis B virus-associated hepatocellular carcinoma: network pharmacology and cell experiments.

Hepatocellular carcinoma (HCC) is a pressing global issue, with Hepatitis B virus (HBV) infection remaining the primary. Emodin, an anthraquinone compound extracted from the natural plant's. This study investigates the molecular targets and possible mechanisms of emodin in treating HBV-related HCC based on network pharmacology and molecular docking and validates the screened molecular targets through in vitro experiments. Potential targets related to emodin were obtained through PubChem, CTD, PharmMapper, SuperPred, and TargetNet databases. Potential disease targets for HBV and HCC were identified using the DisGeNET, GeneCards, OMIM, and TTD databases. A Venn diagram was used to determine overlapping genes between the drug and the diseases. Enrichment analysis of these genes was performed using GO and KEGG via bioinformatics websites. The overlapping genes were imported into STRING to construct a protein-protein interaction network. Cytoscape 3.9.1 software was used for visualizing and analyzing the core targets. Molecular docking analysis of the drug and core targets was performed using Schrodinger. The regulatory effects of emodin on these core targets were validate through in vitro experiments. A total of 43 overlapping genes were identified. GO analysis recognized 926 entries, and KEGG analysis identified 135 entries. The main pathways involved in the KEGG analysis included cancer, human cytomegalovirus infection and prostate cancer. The binding energies of emodin with HSP90AA1, PTGS2, GSTP1, SOD2, MAPK3, and PCNA were all less than -5 kcal/mol. Compared to normal liver tissue, the mRNA levels of XRCC1, MAPK3, and PCNA were significantly elevated in liver cancer tissue. The expression levels of XRCC1, HIF1A, MAPK3, and PCNA genes were closely related to HCC progression. High expressions of HSP90AA1, TGFB1, HIF1A, MAPK3, and PCNA were all closely associated with poor prognosis in HCC. In vitro experiments demonstrated that emodin significantly downregulated the expression of HSP90AA1, MAPK3, XRCC1, PCNA, and SOD2, while significantly upregulating the expression of PTGS2 and GSTP1. This study, based on network pharmacology and molecular docking validation, suggests that emodin may exert therapeutic effects on HBV-related HCC by downregulating the expression of XRCC1, MAPK3, PCNA, HSP90AA1, and SOD2, and upregulating the expression of PTGS2 and GSTP1.

Wang Y ，Li S ，Ren T ，Zhang Y ，Li B ，Geng X ... -  《Frontiers in Cellular and Infection Microbiology》

Understanding apoptotic induction by Sargentodoxa cuneata-Patrinia villosa herb pair via PI3K/AKT/mTOR signalling in colorectal cancer cells using network pharmacology and cellular studies.

Mu BX ，Li Y ，Ye N ，Liu S ，Zou X ，Qian J ，Wu C ，Zhuang Y ，Chen M ，Zhou JY ... -  《-》

Exploring the Targets and Molecular Mechanisms of Curcumin for the Treatment of Bladder Cancer Based on Network Pharmacology, Molecular Docking and Molecular Dynamics.

Curcumin, a phenolic compound derived from turmeric, has demonstrated anti-tumor properties in preclinical models of various cancers. However, the exact mechanism of curcumin in treating bladder cancer remains unclear. This study aimed to elucidate the therapeutic targets and molecular mechanisms of curcumin in the treatment of BC through an integrated approach of network pharmacology, molecular docking, and molecular dynamics simulations. PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction were utilized to acquire targets associated with curcumin, while GeneCards, CTD, DisGeNET, OMIM, and PharmGKB databases were utilized to obtain targets related to bladder cancer. The drug-disease interaction targets were obtained using Venny 2.1.0, and GO and KEGG enrichment analyses were then conducted with the DAVID tool. We constructed a protein-protein interaction (PPI) network and identified tenkey targets. In conclusion, AutoDock Tools 1.5.7 was utilized to conduct molecular docking simulations, followed by additional analysis of the central targets through the GEPIA, HPA, cBioPortal, and TIMER databases. A total of 305 potential anticancer targets of curcumin were obtained. The analysis of GO functional enrichment resulted in a total of 1105 terms, including 786 terms related to biological processes (BP), 105 terms related to cellular components (CC), and 214 terms related to molecular functions (MF). In addition, KEGG pathway enrichment analysis identified 170 relevant signaling pathways. Treating bladder cancer could potentially involve inhibiting pathways like the PI3K-Akt signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, and IL-17 signaling pathway. Activating TNF, ALB, CASP3, and ESR1 while inhibiting AKT1, EGFR, STAT3, BCL2, SRC, and HSP90AA1 can also hinder the proliferation of bladder tumor cells. According to the results of molecular docking, curcumin binds to these central targets in a spontaneous manner, exhibiting binding energies lower than - 1.631 kJ/mol. These findings were further validated at the transcriptional, translational and immune infiltration levels. By utilizing network pharmacology and molecular docking techniques, it was discovered that curcumin possesses diverse effects on multiple targets and pathways for treating bladder cancer. It has the potential to impede the growth of bladder tumor cells by suppressing various pathways including the PI3K-Akt and MAPK signaling pathways, as well as pathways associated with EGFR tyrosine kinase inhibitor resistance and the IL-17 signaling pathway. Curcumin could potentially disrupt the cell cycle advancement in bladder cancer cells by increasing the expression of TNF, ALB, CASP3, and ESR1 while decreasing AKT1, EGFR, STAT3, BCL2, SRC, HSP90AA1, and other targeted genes. These findings reveal the possible molecular pathways through which curcumin exerts its anticancer effects in bladder cancer, and this novel research strategy not only provides an important basis for an in-depth understanding of the anticancer mechanism of curcumin, but also offers new potential drugs and targets for the clinical treatment of bladder cancer. Therefore, this study is of great scientific significance and practical application value for promoting the development of bladder cancer therapeutic field. This finding provides strong support for the development of novel, safe and effective drugs for bladder cancer treatment.

Li J ，Feng S ，Wang X ，Zhang B ，He Q ... -  《-》

Exploring the therapeutic mechanism of curcumin in prostate cancer using network pharmacology and molecular docking.

Curcumin, a phenolic compound extracted from turmeric rhizomes, exhibits antitumour effects in preclinical models of tumours. However, its mechanism of action in prostate cancer remains unclear. Exploring the molecular mechanisms of curcumin in prostate cancer based on network pharmacology and molecular docking provides a new theoretical basis for prostate cancer treatment. Using tools such as PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction, we obtained information on curcumin-related targets. We comprehensively collected prostate cancer-related targets from several databases, including GeneCards, CTD, DisGeNET, OMIM, and PharmGKB. Cross-cutting drug-disease targets were then derived by screening using the Venny 2.1.0 tool. Subsequently, we used the DAVID platform to perform in-depth GO and KEGG enrichment analyses of the drug-disease-shared targets. To construct a PPI network map of the cross-targets and screen the 10 core targets, we combined the STRING database and Cytoscape 3.7.2. Molecular docking experiments were performed using AutoDockTools 1.5.7 software. Finally, we used several databases such as GEPIA, HPA, cBioPortal, and TIMER to further analyse the screened core targets in detail. We identified 307 key targets of curcumin in cancer treatment. After GO functional enrichment analysis, we obtained 1119 relevant entries, including 782 biological progression (BP) entries, 112 cellular component (CC) entries, and 225 molecular function (MF) entries. In addition, KEGG pathway enrichment analysis revealed 126 signalling pathways, which were mainly involved in the cancer pathway, such as lipid and atherosclerosis pathway, PI3K-Akt signal pathway, MAPK signal pathway, Ras signal pathways, and chemical carcinogenesis-reactive oxygen species. By applying Cytoscape 3.7.2 software, we identified SRC, PIK3R1, STAT3, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1 as core targets. Molecular docking experiments showed that the binding energies of curcumin to these core targets were all below -1.85 kJ mol-1, which fully demonstrated that curcumin could spontaneously bind to these core targets. Finally, these results were validated at multiple levels, including mRNA expression, protein expression, and immune infiltration. Through in-depth network pharmacology and molecular docking studies, we have found that curcumin may have anticancer potential by upregulating the expression of PIK3R1 and STAT3, and downregulating the binding ability of molecules such as SRC, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1. In addition, curcumin may interfere with the cyclic process of prostate cancer cells by inhibiting key signalling pathways such as the PI3K-Akt signalling pathway, MAPK signalling pathway, and Ras, thereby inhibiting their growth. This study not only reveals the potential molecular mechanism of curcumin in the treatment of prostate cancer but also provides an important theoretical basis for subsequent research.

Li J ，Wang X ，Xue L ，He Q ... -  《Heliyon》