Objective:To explore the regulatory mechanism of ginsenoside Rh1 on breast cancer cell extravasation based on CCL20-CCR6.Methods:In 2021,a total of 34 patients with breast cancer were treated in Baoding First Central ...Objective:To explore the regulatory mechanism of ginsenoside Rh1 on breast cancer cell extravasation based on CCL20-CCR6.Methods:In 2021,a total of 34 patients with breast cancer were treated in Baoding First Central Hospital.During hospitalization,pathological examinations were performed,and all the patients were diagnosed with invasive ductal carcinoma.Out of the 34 cases,16 cases were found to have CCR6 expression in breast cancer tissues,in which they were recorded as the CCR6 expression group,whereas 18 cases did not have CCR6 expression;these cases were recorded as the CCR6 non-expression group.During the same period,21 normal patients were selected as the control group.The peripheral blood CCL20 level and the expression of CCR6 on the surface of CD3+T lymphocytes were analyzed.The extracts of cancer cells were collected,purified,and cultured,and the effect of ginsenoside Rh1 on the invasion and metastasis of breast cancer cells was analyzed.Results:The peripheral blood CCL20 level in the CCR6 expression group was significantly higher than that in the CCR6 non-expression group and the control group,in which p<0.05,indicating that the difference was statistically significant;at 12,24,and 48 hours,the cell survival rate of each dose group was significantly higher than that of the blank control group and the dimethyl sulfoxide(DMSO)group(p<0.05).At 48 hours,comparing the low-dose group with the high-dose group,the cell survival rate significantly decreased(p<0.05).Compared with the blank control group and DMSO group,the invasion ability of breast cancer cells could be reduced in both,high-and medium-dose groups,where p<0.05,indicating that the difference was statistically significant.Conclusion:CCL20 may play a role in the pathogenesis of certain breast cancers,and ginsenoside Rh1 can effectively regulate the invasion and migration of breast cancer cells.展开更多
Forty-nine microbial strains were used to screen their ability for the microbiological transforma-tion of ginsenoside Rg1. Aspergillus niger (3.1858) and Absidia coerulea (3.3538) were found to convert ginsenoside Rg1...Forty-nine microbial strains were used to screen their ability for the microbiological transforma-tion of ginsenoside Rg1. Aspergillus niger (3.1858) and Absidia coerulea (3.3538) were found to convert ginsenoside Rg1 efficiently to less polar metabolites. Preparative scale transformation with both fungi Absidia coerulea (3.3538) and Aspergillus niger (3.1858) have resulted in the production of one same metabolite (MT1). Its structure was char-acterized as 6-O-b-D-glucopyranosyl-20(S)-protopanaxatriol (Ginsenoside Rh1) on the basis of its TOF-MS and 1H, 13C NMR spectral data. The biotransformation kinetic curves for Ginsenoside Rg1 and MT1 were reported for the first time, and the biotransformation pathway was proposed.展开更多
A novel saponin was isolated from the transformed products of ginsenoside Rh1 by Bacillus subtilis. It's structure was determined to be 3-O-β-D-glucopyranosyl-6-O-β-D-gluco- pyranosyl-20 (S)-protopanaxatriol on ...A novel saponin was isolated from the transformed products of ginsenoside Rh1 by Bacillus subtilis. It's structure was determined to be 3-O-β-D-glucopyranosyl-6-O-β-D-gluco- pyranosyl-20 (S)-protopanaxatriol on the basis of the spectral data.展开更多
Objective:Ginsenoside Rh1(G-Rh1)has been confirmed to inhibit the growth of breast cancer and colon cancer,but its therapeutic effect on hepatocellular carcinoma(HCC)is unclear.This study investigates the therapeutic ...Objective:Ginsenoside Rh1(G-Rh1)has been confirmed to inhibit the growth of breast cancer and colon cancer,but its therapeutic effect on hepatocellular carcinoma(HCC)is unclear.This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism.Methods:Bioinformatics methods were used to analyze glucocorticoid receptor(GR)expression and the tumor microenvironment in HCC tissues from HCC patients.The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice.Additionally,the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry,the GR and major histocompatibility complex class-I(MHC-I)expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting,and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell(DC)maturation and CD8+T cell activation.Results:GR expression was upregulated in HCC tissues,and high GR expression was associated with a worsened immune microenvironment.In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells,while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice.Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment,thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8+T cells,mature DCs,and MHC-I-positive cells.MHC-I was upregulated by G-Rh1 via GR suppression.Moreover,overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells,as well as the maturation of DCs and the activation of CD8+T cells.Conclusion:G-Rh1 can regulate the immune microenvironment of HCC by targeting GR,thus increasing the antitumor effect of lenvatinib.展开更多
Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high perf...Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography–tandem mass spectrometry(LC–MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile,urine, and feces after oral administration(25 mg/kg). Calibration curves offered satisfactory linearity(r40.995)within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80–120%. The excretion recoveries of Rg1, ginsenoside Rh1(Rh1), and protopanaxatriol(Ppt) in bile,urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile.Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.展开更多
基金supported by grants from The Medical Science Research Project of Hebei Province(20220282)the Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province.
文摘Objective:To explore the regulatory mechanism of ginsenoside Rh1 on breast cancer cell extravasation based on CCL20-CCR6.Methods:In 2021,a total of 34 patients with breast cancer were treated in Baoding First Central Hospital.During hospitalization,pathological examinations were performed,and all the patients were diagnosed with invasive ductal carcinoma.Out of the 34 cases,16 cases were found to have CCR6 expression in breast cancer tissues,in which they were recorded as the CCR6 expression group,whereas 18 cases did not have CCR6 expression;these cases were recorded as the CCR6 non-expression group.During the same period,21 normal patients were selected as the control group.The peripheral blood CCL20 level and the expression of CCR6 on the surface of CD3+T lymphocytes were analyzed.The extracts of cancer cells were collected,purified,and cultured,and the effect of ginsenoside Rh1 on the invasion and metastasis of breast cancer cells was analyzed.Results:The peripheral blood CCL20 level in the CCR6 expression group was significantly higher than that in the CCR6 non-expression group and the control group,in which p<0.05,indicating that the difference was statistically significant;at 12,24,and 48 hours,the cell survival rate of each dose group was significantly higher than that of the blank control group and the dimethyl sulfoxide(DMSO)group(p<0.05).At 48 hours,comparing the low-dose group with the high-dose group,the cell survival rate significantly decreased(p<0.05).Compared with the blank control group and DMSO group,the invasion ability of breast cancer cells could be reduced in both,high-and medium-dose groups,where p<0.05,indicating that the difference was statistically significant.Conclusion:CCL20 may play a role in the pathogenesis of certain breast cancers,and ginsenoside Rh1 can effectively regulate the invasion and migration of breast cancer cells.
文摘Forty-nine microbial strains were used to screen their ability for the microbiological transforma-tion of ginsenoside Rg1. Aspergillus niger (3.1858) and Absidia coerulea (3.3538) were found to convert ginsenoside Rg1 efficiently to less polar metabolites. Preparative scale transformation with both fungi Absidia coerulea (3.3538) and Aspergillus niger (3.1858) have resulted in the production of one same metabolite (MT1). Its structure was char-acterized as 6-O-b-D-glucopyranosyl-20(S)-protopanaxatriol (Ginsenoside Rh1) on the basis of its TOF-MS and 1H, 13C NMR spectral data. The biotransformation kinetic curves for Ginsenoside Rg1 and MT1 were reported for the first time, and the biotransformation pathway was proposed.
文摘A novel saponin was isolated from the transformed products of ginsenoside Rh1 by Bacillus subtilis. It's structure was determined to be 3-O-β-D-glucopyranosyl-6-O-β-D-gluco- pyranosyl-20 (S)-protopanaxatriol on the basis of the spectral data.
基金supported by the Natural Science Foundation of Shandong Province(No.ZR2020MH39)。
文摘Objective:Ginsenoside Rh1(G-Rh1)has been confirmed to inhibit the growth of breast cancer and colon cancer,but its therapeutic effect on hepatocellular carcinoma(HCC)is unclear.This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism.Methods:Bioinformatics methods were used to analyze glucocorticoid receptor(GR)expression and the tumor microenvironment in HCC tissues from HCC patients.The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice.Additionally,the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry,the GR and major histocompatibility complex class-I(MHC-I)expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting,and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell(DC)maturation and CD8+T cell activation.Results:GR expression was upregulated in HCC tissues,and high GR expression was associated with a worsened immune microenvironment.In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells,while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice.Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment,thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8+T cells,mature DCs,and MHC-I-positive cells.MHC-I was upregulated by G-Rh1 via GR suppression.Moreover,overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells,as well as the maturation of DCs and the activation of CD8+T cells.Conclusion:G-Rh1 can regulate the immune microenvironment of HCC by targeting GR,thus increasing the antitumor effect of lenvatinib.
基金supported by the National Natural Science Foundation of China(Nos.81173578 and 81573493)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(No.Z141102004414062)+2 种基金National 863 Program of China(No.2014AA020803)the PUMC Youth Fund and Fundamental Research Funds for the Central Universities(No.3332015136)the Fundamental Research Funds for Central Public Institutes(No.2015CX12)
文摘Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography–tandem mass spectrometry(LC–MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile,urine, and feces after oral administration(25 mg/kg). Calibration curves offered satisfactory linearity(r40.995)within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80–120%. The excretion recoveries of Rg1, ginsenoside Rh1(Rh1), and protopanaxatriol(Ppt) in bile,urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile.Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.