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Objective:To investigate the mechanism of bladder cancer treatment by using Scutellaria barbata and Codonopsis pilosula drug pair through network pharmacology. Methods:The drug composition of the drug pair was screened using TCMSP, and their action targets were predicted using Swiss Target Prediction. GeneCards was used to obtain disease targets of bladder cancer, and venny 2.1 was used to obtain intersection targets. PPI analysis was performed using STRING, and a network diagram was constructed using Cytoscape. GO and KEGG analysis were conducted using Metascape. A drug-target-pathway network map was constructed using Cytoscape software. Nude mice were randomly divided into a model group and a treatment group to establish a bladder cancer mouse model. On the 8th day after model formation, the mice in the model group were administered intragastrically with a dose of 342.86 mg/kg, 0.2 ml, twice/day. On the 28th day after modeling, the tumor size of nude mice was measured. Prostaglandin G/H Synthetase 2 (PTGS2), PTGS1, Nuclear Receptor Coactivator 2 (NCOA2), Retinoic Acid X Receptor α (RXRA), Progesterone Receptor (PGR), Mitogen-Activated Protein Kinase 1 (MAPK1), Reticuloendothelial Proliferation virus oncogene homology A (RELA), and Akt1 levels were detected by enzyme-linked immunosorbent assay.Results:The results show that 45 active components of the drug pair directly acted on 187 disease targets through multiple pathways to treat bladder cancer, in which Quercetin, luteolin, wogonin, 7-Methoxy-2-methyl isoflavone, baicalein, beta-sitosterol, Stigmastero, and other core ingredients, as well as PTGS2, PTGS1, NCOA2, RXRA, PGR, MAPK1, RELA, and Akt1 are critical targets. The results of gene function annotation analysis show that the biological processes most likely related to crossover genes mainly involved responses to hormones, cell responses to lipids, responses to foreign stimuli, and responses to bacterial molecules. The cell components mainly involves transcription regulatory complexes, membrane rafts, membrane microregions, and RNA polymerase Ⅱ transcriptional regulatory complexes, etc. The molecular functions mainly involve transcription factor binding, DNA-binding transcription factor binding, RNA polymerase Ⅱ specific DNA-binding transcription factor binding, nuclear receptor activity, ligand-activated transcription factor activity, etc. The results of pathway enrichment analysis suggests that the main signaling pathways are AGE-RAGE, IL-17, PI3K-Akt, TNF, MAPK, HIF-1, apoptosis, p53, toll-like receptor, etc. Animal experiments show that the Scutellaria barbata and Codonopsis pilosula drug pair can significantly improve tumor size and also improve the expression levels of PTGS2, PTGS1, NCOA2, RXRA, PGR, MAPK1, RELA, and Akt1. Conclusions:The Scutellaria barbata and Codonopsis pilosula drug pair can regulate PTGS2, PTGS1, NCOA2, RXRA, PGR, MAPK1, RELA, and Akt1 and other diseases mainly through the regulation of AGE-RAGE, IL-17, PI3K-Akt, TNF, MAPK, HIF-1, apoptosis, p53, toll-like receptor, and other signaling pathways. Targeting enzyme activity and cell apoptosis can treat bladder cancer by regulating these biological processes.
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Scutellaria barbata D. Don is widely used in TCM clinical practice, so it is important to delve the information of its system biology. In this paper, we integrate its natural compounds and genomics information. The Herb-Prince complex networks algorithm is used to delve potential associated genes, gene families and KEGG signal pathways for Scutellaria barbata D. Don, and the information is verified by literature. The top 100 genes, 4 gene families and 10 KEGG signaling pathways were found. The related results are highly consistent with the clinical and pharmacological studies of Scutellaria barbata D. Don, which provide decision support for researchers to study pharmacological activities of Scutellaria barbata D. Don at the molecular level.
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Objective: To explore the active compounds and integrative mechanism of Scutellaria barbata in treatment of cancer by using network pharmacology. Methods: The active components were screened by five rules of durability. The target proteins of S. barbata were obtained by molecular docking. The main diseases related to S. barbata were obtained by Comparative Toxicogenomics Database (CTD). Then, the compound-target-disease interaction network was built using cytoscape 3.40. After protein-protein interaction analysis, Biological Information Annotation Databases (DAVID) was used to analyze the biological metabolic pathway of target proteins. Results: A total of 72 compounds from S. barbata acted with more than 14 cancer-related targets, and diterpenoids including scutelinquninne D, barbatellarine E, and scutebarbatines A were the main active molecules of S. barbata. Network analysis showed that the active compounds of S. barbata can regulate VEGF signaling pathway, Fc epsilon RI signaling pathway, and FoxO signaling pathway through acting with the key targets protein, such as protein tyrosine phosphatase 1B (PTP1B), carbonic anhydrase 2 (CA2), cyclic protein dependent kinases 2 (CDK2), retinoic acid α receptor (RXRA) and so on. Finally, S. barbata regulated the process of inflammation and tumor angiogenesis for its anticancer effect. Conclusion: S. barbata can show the multi-target and multi-pathway synergistic antitumor activity through anti-inflammation and inhibiting tumor angiogenesis.
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<p><b>OBJECTIVE</b>To investigate the effect of the ethanol extract of Scutellaria barbata D. Don (EESB) on colorectal cancer (CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro.</p><p><b>METHODS</b>In vivo experiment, CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation, twenty mice were randomly divided into EESB-treated group (n=10) and control group (n=10) by a random number table, and were given with intra-gastric administration of 2 g/kg EESB or saline, 5 days a week for 16 days, respectively. At the end of experiment, tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry (IHC) assay. In vitro study, HT-29 cells were treated with 0, 0.5, 1.5, 2.5 mg/mL EESB for 24 h. At the end of the treatment, the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and colony formation assay, respectively. The mRNA expression of c-Myc, Survivin and adenomatous polyposis coli (APC) was examined by reverse transcription-polymerase chain reaction (RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc, Survivin, APC, and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting.</p><p><b>RESULTS</b>EESB significantly reduced tumor weight in CRC xenografts mice, compared with the control group (P<0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues (P<0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner (P<0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells (P<0.05). In addition, RT-PCR assay showed that EESB decreased the mRNA expression of c-Myc and Survivin and increased APC expression, both in tumor tissues of CRC xenograft mice and HT-29 cells (P<0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin, c-Myc and Survivin, as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells (P<0.05).</p><p><b>CONCLUSIONS</b>EESB significantly reduced tumor growth in CRC xenografts mice, and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway, which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.</p>
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Objective To determine the optimum harvest time of Scutellaria barbata D.Don with flavonoids contents as the index. Methods The content of total flavonoids in Scutellaria barbata D. Don was determined by ultraviolet-visible spectrophotometry with scutellarin as standard control, and scutellarin and cosmosiin in Scutellaria barbata D. Don were determined by HPLC. Results The contents of total flavonoids and scutellarin in Scutellaria barbata D.Don of different harvest time were complied with the quality standards in the China Pharma Copoeia, and reached the peakin blossom . The contents of total flavonoids, scutellarin and cosmosiin were (45.74±0.95) ,(5.58±0.16 ) and (17.39±0.42) mg?g-1 , respectively. Conclusion The Scutellaria Barbata D.Don may be collected at the flowering time with luxuriant foliage.
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Objective: To investigate the constituents in the aerial parts of Scutellaria barbata. Methods: The isolation and purification of the compounds were performed by AB-8 macroporous adsorption resin, silica gel, polyamide and Sephadex LH-20 column chromatography, and their structures were determined on physicochemical characters and spectroscopic data. Results: Fourteen compounds were separated and elucidated as hispidulin-7-O-β-D-methylgluzcuronide (1), apigenin (2), scutellarin (3), scutellarein (4), luteolin (5), scutellarein-7-O-β-D-glucuronide methyl ester (6), isoscutellarein-8-O-β-D-glucuronide-6″-methyl ester (7), apigenin-7-O-β-D-glucuronide-6″-methyl ester (8), 4'-hydroxywogonin (9), 4',5-dihydroxy-3',5',6,7-tetramethoxyflavone (10), isoscutellarein (11), 6-hydroxyluteolin (12), 5-hydroxy-6,7,3',4'-tetramethoxyflavone (13), salvigenin (14). Conclusion: Compound 7 is isolated from Lamiaceae for the first time, compounds 1 and 13 are for the first time isolated from the genus Scutellaria, and compounds 6 and 12 are for the first time obtained from S. barbata.
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Objective: To study the chemical constituents from the whole plant of Scutellaria barbata. Methods: The constituents were isolated and purified by using various column chromatographic techniques including silica gel column chromatography, MCI, ODS, and Sephadex LH-20, the structures were identified by spectroscopic analyses including HR-ESI-MS, NMR, and 2D-NMR. Results: A new neoclerodane diterpenoid named scutelinquanine E was isolated from the whole plant of S. barbata, and its structrue was identified as (13R)-7β-hydroxy-8,13-epoxy-6α,11β-diacetoxy-ent-clerodan-3-en-15, 16-olide. Conclusion: Compound 1 is a new neoclerodane diterpenoid named as scutellone J.
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Objective BALB/C mice were inoculated subcutaneously with hepatoma 22 (H22) cells, and the treatment effect of thalidomide and intratumor injection of ethanol extract of Scutellaria Barbata (SB) on tumor growth were evaluated. Methods In vitro, mouse H22 liver cells were cultivated, and H22 cells in the logarithmic growth phase were tested. SB was extracted in the ethanol recirculation. A total of 28 BALB/C male mice inoculated subcutaneously with H22 cells were randomly divided into 4 groups, 7 mice per group. Group A:intragastric administration with thalidomide. Group B:SB intratumor injection. Group C:combination of thalidomide and SB with the same administration as Group A and Group B. Group D (control group):1% Ethanol 0.2～0.5 mL intratumor injection. Tumor volumes of four groups were observed and the tumors were weighed. The microvessel densities (MVD) of all transplantation tumors were measured by immunohistochemical staining with anti-CD31 monoclonal antibody. Results There were statistically significant differences between Group C and Group A (P 0.05). The studies showed statistically differences between Group C and Group A (P
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Isolating and determining molecule structure of compounds with inhibition and killing effect on cancer cell growth of Scutellaria barbata D. Don showed that the first compounds were 8, 13- epoxy-3-en-7-hydroxy-6, 11- O-dibenzoyl-15, 16 clerodanolid. These compounds were a diterpen with high activity of cancer cell growth inhibitor with IC50 value equal 2.15 – 8.3 µM. The compound showed strongest activity on breast cancer (2.15µM (MCF7)) and less activity on carcinoma (8.3 µM (KB). However, the compound showed relative similar activity on prostate cancer and lung cancer cell lines. Thus, the above compound showed cancer cell growth inhibition and killing activity at different level depending on cancer kind