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OBJECTIVE: Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G-Rg5) is a minor ginsenoside extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti-tumor properties. The objective of current study was to explore the mechanism of G-Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology. METHODS: Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G-Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G-Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G-Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G-Rg5 and hub targets. The hub genes were imported into the Kaplan-Meier Plotter online database for survival analysis. RESULTS: A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K-Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma-associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets-pathways network analyses. The results of molecular docking showed that the binding energies were all less than -7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients. CONCLUSION: This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.
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Neoplasias Óseas , Medicamentos Herbarios Chinos , Ginsenósidos , Osteosarcoma , Humanos , Simulación del Acoplamiento Molecular , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Osteosarcoma/tratamiento farmacológico , Neoplasias Óseas/tratamiento farmacológicoRESUMEN
Abstract Objective Tongue squamous cell carcinoma (TSCC) is an oral cancer, with high malignancy and frequent early migration and invasion. Only a few drugs can treat tongue cancer. Ginsenoside Rd is a ginseng extract with anti-cancer effects. Many noncoding RNAs are abnormally expressed in tongue cancer, thus influencing its occurrence and development. H19 and miR-675-5p can promote cancer cell growth. This study aimed to analyze the regulation effect of ginsenoside Rd on H19 and miR-675-5p in tongue cancer. Methodology We used CCK8 and flow cytometry to study the growth and apoptosis. Transwell assay was used to assess invasion; wound-healing assay to assess migration; and colony formation assays to test the ability of cells to form colonies. H19, miR-675-5p, and CDH1 expressions were analyzed by qPCR. E-cadherin expression was detected using western blot. CRISPR/cas9 system was used for CDH1 knockout. Results Ginsenoside Rd inhibited the growth and increased the apoptosis of SCC9 cells. Ginsenoside Rd also inhibited the migration and invasion of SCC9 cells. H19 and miR-675-5p were highly expressed, while CDH1 and E-cadherin expressions were low. H19 and miR-675-5p promoted SCC9 metastasis. In contrast, CDH1 and E-cadherin inhibited the metastasis of SCC9 cells. Bioinformatics analysis showed that miR-675-5p was associated with CDH1. H19 and miR-675-5p expressions decreased after ginsenoside Rd treatment, while CDH1 and E-cadherin expressions increased. Conclusions Ginsenoside Rd inhibits tongue cancer cell migration and invasion via the H19/miR-675-5p/CDH1 axis.
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BACKGROUND: This work aimed to investigate the inhibitory effect of regorafenib in combination with ginsenoside on the growth of HepG2 liver cancer cells. METHODS: HepG2 liver cancer cells were divided into blank control group, regorafenib single-drug group, ginsenoside single-drug group, and regorafenib/ginsenoside combination group. Cells in the regorafenib single-drug group were treated with regorafenib at 0.25 mg/L, 0.5 mg/L, and 1 mg/L, respectively, while cells in the ginsenoside single-drug group were treated with ginsenoside at 5.0 mg/L, 10.0 mg/L, and 20.0 mg/L, respectively. HepG2 cell proliferation, expression of survivin mRNA, and the apoptotic effector caspase-3 in HepG2 liver cancer cells were assessed. RESULTS: An inhibitory effect on the growth of HepG2 liver cancer cells was observed for both the single-drug therapies and the combination therapy. The synergistic inhibitory effect presented by the combination therapy was dependent on the gradient concentration and treatment time. RT-qPCR results showed that both regorafenib and ginsenoside significantly reduced the expression of survivin mRNA in HepG2 liver cancer cells and the expression level of survivin mRNA in the regorafenib/ginsenoside combination group was much lower than those in the regorafenib single-drug group and ginsenoside single-drug group. The two drugs demonstrated synergistic inhibitory effect when used in combination. CONCLUSIONS: The findings in this study offered a theoretical insight into clinical use of regorafenib and ginsenoside for treatment of liver cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Caspasa 3/biosíntesis , Ginsenósidos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea/farmacología , Piridinas/farmacología , Survivin/biosíntesis , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Ginsenósidos/administración & dosificación , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Compuestos de Fenilurea/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/administración & dosificación , Survivin/genética , Survivin/metabolismoRESUMEN
Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1β, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1β by suppressing the increase in IL-1β, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1β-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1β to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Condrocitos/efectos de los fármacos , Ginsenósidos/farmacología , Interleucina-1beta/efectos de los fármacos , Proteína Accesoria del Receptor de Interleucina-1/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Dinoprostona/metabolismo , Supervivencia Celular/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Dolor de la Región Lumbar/metabolismo , Óxido Nítrico Sintasa/metabolismo , Condrocitos/citología , Condrocitos/metabolismo , Ginsenósidos/metabolismo , Ciclooxigenasa 2/metabolismo , Agrecanos/metabolismo , Interleucina-1beta/metabolismo , Ubiquitinación , Núcleo Pulposo/citología , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/metabolismo , Inflamación/metabolismoRESUMEN
Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.
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Animales , Masculino , Ratones , Dieta Alta en Grasa , Ginsenósidos/farmacología , Trastornos del Metabolismo de la Glucosa/prevención & control , Obesidad/complicaciones , Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/metabolismo , Resistencia a la Insulina , Obesidad/metabolismo , Transducción de Señal , Factores de TiempoRESUMEN
Ginsenoside Rg1, one of the most notable active components of Panax ginseng, has been widely reported to exert anti-inflammatory actions. This study aimed to reveal whether ginsenoside Rg1 also exhibits beneficial roles against lipopolysaccharide (LPS)-induced apoptosis and inflammation in human renal tubular epithelial cells, and to evaluate the potential role of the component on tubulointerstitial nephritis treatment. HK-2 cells were treated with various doses of ginsenoside Rg1 (0, 50, 100, 150, and 200 μM) in the absence or presence of 5 μg/mL LPS. Thereafter, CCK-8 assay, flow cytometry, western blot, migration assay, reactive oxygen species (ROS) assay, and ELISA were carried out to respectively assess cell viability, apoptosis, migration, ROS activity, and the release of inflammatory cytokines. As a result, ginsenoside Rg1 protected HK-2 cells from LPS-induced injury, as cell viability was increased, cell apoptosis was decreased, and the release of MCP-1, IL-1β, IL-6, and TNF-α was reduced. Ginsenoside Rg1 functioned to HK-2 cells in a dose-dependent manner, and the 150 μM dose exhibited the most protective functions. Ginsenoside Rg1 had no significant impact on cell migration and ROS activity, while it alleviated LPS-induced ROS release and migration impairment. Furthermore, the down-regulations of p-PI3K, p-AKT, and up-regulations of PTEN, p-IκBα, p-p65, Bcl-3 induced by LPS were recovered to some extent after ginsenoside Rg1 treatment. In conclusion, ginsenoside Rg1 protects HK-2 cells against LPS-induced inflammation and apoptosis via activation of the PI3K/AKT pathway and suppression of NF-κB pathway.
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Humanos , Lipopolisacáridos , Apoptosis/efectos de los fármacos , Ginsenósidos/farmacología , Células Epiteliales/efectos de los fármacos , Túbulos Renales/citología , Antiinflamatorios/farmacología , Ensayo de Inmunoadsorción Enzimática , Línea Celular , Supervivencia Celular/efectos de los fármacos , Western Blotting , Reproducibilidad de los Resultados , Análisis de Varianza , Citocinas/análisis , Citocinas/efectos de los fármacos , Ensayos de Migración CelularRESUMEN
Background: Ginsenoside is the most important secondary metabolite in ginseng. Natural sources of wild ginseng have been overexploited. Although root culture can reduce the length of the growth cycle of ginseng, the number of species of ginsenosides is reduced and their contents are lower in the adventitious roots of ginseng than in the roots of ginseng cultivated in the field. Results: In this study, 147 strains of ß-glucosidase-producing microorganisms were isolated from soil. Of these, strain K35 showed excellent activity for converting major ginsenosides into rare ginsenosides, and a NCBI BLAST of its 16S rDNA gene sequence showed that it was most closely related to Penicillium sp. (HQ608083.1). Strain K35 was used to ferment the adventitious root extract, and the fermentation products were analyzed by high-performance liquid chromatography. The results showed that the content of the rare ginsenoside CK was 0.253 mg mL-1 under the optimal converting conditions of 9 d of fermentation at pH 7.0 in LL medium, which was significantly higher than that in the adventitious roots of ginseng. Conclusion: These findings may not only solve the problem of low productivity of metabolite in ginseng root culture but may also result in the development of a new valuable method of manufacturing ginsenoside CK.
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beta-Glucosidasa/metabolismo , Raíces de Plantas/metabolismo , Ginsenósidos/metabolismo , Panax/metabolismo , Penicillium , Biotransformación , Cromatografía Líquida de Alta Presión , Raíces de Plantas/química , Reactores Biológicos , Ginsenósidos/aislamiento & purificación , Fermentación , Panax/crecimiento & desarrollo , Panax/químicaRESUMEN
About 40 different types of ginsenoside (ginseng saponin), a major pharmacological component of ginseng, have been identified along with their physiological activities. Among these, compound K has been reported to prevent the development of and the metastasis of cancer by blocking the formation of tumors and suppressing the invasion of cancerous cells. In this study, ginsenoside Rb1 was converted into compound K via interaction with the enzyme secreted by ¥â-glucosidase active bacteria, Leuconostoc citreum LH1, extracted from kimchi. The optimum time for the conversion of Rb1 to compound K was about 72 hrs at a constant pH of 6.0 and an optimum temperature of about 30¨¬C. Under optimal conditions, ginsenoside Rb1 was decomposed and converted into compound K by 72 hrs post-reaction (99 percent). Both TLC and HPLC were used to analyze the enzymatic reaction. Ginsenoside Rb1 was consecutively converted to ginsenoside Rd, F2, and compound K via the hydrolyses of 20-C ¥â-(1 ¡æ 6)-glucoside, 3-C ¥â-(1 ¡æ 2)glucoside, and 3-C ¥â-glucose of ginsenoside Rb1.
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Cromatografía , Enzimas Reparadoras del ADN/análisis , Técnicas In Vitro , Leuconostoc/enzimología , Leuconostoc/aislamiento & purificación , Panax/enzimología , Estructuras de las PlantasRESUMEN
About 40 different types of ginsenoside (ginseng saponin), a major pharmacological component of ginseng, have been identified along with their physiological activities. Among these, compound K has been reported to prevent the development of and the metastasis of cancer by blocking the formation of tumors and suppressing the invasion of cancerous cells. In this study, ginsenoside Rb1 was converted into compound K via interaction with the enzyme secreted by ß-glucosidase active bacteria, Leuconostoc citreum LH1, extracted from kimchi. The optimum time for the conversion of Rb1 to compound K was about 72 hrs at a constant pH of 6.0 and an optimum temperature of about 30°C. Under optimal conditions, ginsenoside Rb1 was decomposed and converted into compound K by 72 hrs post-reaction (99%). Both TLC and HPLC were used to analyze the enzymatic reaction. Ginsenoside Rb1 was consecutively converted to ginsenoside Rd, F2, and compound K via the hydrolyses of 20-C ß-(1 â 6)-glucoside, 3-C ß-(1 â 2)-glucoside, and 3-C ß-glucose of ginsenoside Rb1.
RESUMEN
About 40 different types of ginsenoside (ginseng saponin), a major pharmacological component of ginseng, have been identified along with their physiological activities. Among these, compound K has been reported to prevent the development of and the metastasis of cancer by blocking the formation of tumors and suppressing the invasion of cancerous cells. In this study, ginsenoside Rb1 was converted into compound K via interaction with the enzyme secreted by -glucosidase active bacteria, Leuconostoc citreum LH1, extracted from kimchi. The optimum time for the conversion of Rb1 to compound K was about 72 hrs at a constant pH of 6.0 and an optimum temperature of about 30ºC. Under optimal conditions, ginsenoside Rb1 was decomposed and converted into compound K by 72 hrs post-reaction (99%). Both TLC and HPLC were used to analyze the enzymatic reaction. Ginsenoside Rb1 was consecutively converted to ginsenoside Rd, F2, and compound K via the hydrolyses of 20-C -(1 6)-glucoside, 3-C -(1 2)glucoside, and 3-C -glucose of ginsenoside Rb1.