For making use of Ginseng resources that exhibit an antitumor activity and for finding new anticancer drugs, three new fatty acid ester compounds： 3/β-acetoxy panaxadiol （ Ⅰ ）, 3β-palmitic acid aceloxy panaxadi...For making use of Ginseng resources that exhibit an antitumor activity and for finding new anticancer drugs, three new fatty acid ester compounds： 3/β-acetoxy panaxadiol （ Ⅰ ）, 3β-palmitic acid aceloxy panaxadiol （ Ⅱ ） , and 3β-octadecanoic acid aceloxy panaxadiol（ Ⅰ , Ⅱ, and m） were synthesized with panaxadiol, diacetyl oxide, palmityl chloride and stearyl chloride, and their structures were determined via MS, ^13C NMR, IR, TLC, and so on. The molar yields of the three compounds are 75.14%, 79. 08%, and 72. 57%, respectively. Meanwhile, the antitumor activity of the three new panaxadiol fatty acid ester derivatives and panaxadiol was compared by using the method of MTT. Tumor cell used was Vero cell line. Positive control was 5-FU, blank was an RPMI1640 culture medium, negative control was an RPMI1640 culture medium and the solvent for drugs to be tested. Compound Ⅰ has the strongest antitumor activity followed by panaxadiol; compounds Ⅱ and Ⅲ have similar and weakest antitumor activities. Furthermore, the antitumor activities of the panaxadiol fatty acid ester derivatives show positive correlation with the concentration of the test group, but show no relationship with the molecular weight of fatty acid. The methods that are used to synthesize the three compounds with high yields and strong antitumor activities are simple and show a great potential for meeting the needs of industrial manufacture of these drugs.展开更多
28 Derivatives of panaxadiol(PD)and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells,of which 17 derivatives inhibited HBV DNA replication.Compounds 4,9,10,14,and 15 showed m...28 Derivatives of panaxadiol(PD)and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells,of which 17 derivatives inhibited HBV DNA replication.Compounds 4,9,10,14,and 15 showed moderate activity against HBV DNA replication with IC50 values ranged from 7.27 to 28.21 lM compared with PD.In particular,3-O-20-thenoyl panaxadiol(4)inhibited not only HBV DNA replication(IC50=16.5 lM,SI[115.7)but also HBsAg(IC50=30.8 lM,SI[62.0)and HBeAg(IC50=18.2 lM,SI[105.14)secretions.Their structure–activity relationships were discussed for guiding future research toward the discovery of new anti-HBV agents.展开更多
BACKGROUND Ulcerative colitis(UC),a chronic and challenging condition,necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications...BACKGROUND Ulcerative colitis(UC),a chronic and challenging condition,necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications.Traditional Chinese medicine(TCM),known for its multi-stage and multi-targeted approach,has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment.Panax ginseng(P.ginseng),a commonly used remedy for UC in TCM,exemplifies this potential,although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated,highlighting the need for further research to unlock its full potential as a treatment option.AIM To investigate the key constituents and biological pathways through which P.ginseng exerts therapeutic effects on UC.METHODS Network pharmacology investigated the UC-alleviating mechanism of P.ginseng,including“active ingredient-target-disease”network analysis,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Panaxadiol(PD;active ingredient of P.ginseng)was tested in a mouse model of 3%dextran sulfate sodium-induced UC,with assessments of body weight,Disease Activity Index scores,and colon length.Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining,immunohistochemistry,real time-quantitative PCR,and western blotting.RESULTS By integrating and analyzing the targets of P.ginseng and UC,15 critical hub genes were discovered.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling.Among the 10 main active ingredients identified as potentially effective,PD was most abundant and was validated in vivo to mitigate weight loss,reduce Disease Activity Index scores,and prevent colon shortening.PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators.In addition,PD increased expression of mucin and tight junction proteins.Ultimately,PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK,while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.CONCLUSION PD alleviates colitis and aids intestinal barrier repair,partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways.These findings also suggest new research methods for treatment of UC with TCM.展开更多
Objective： To investigate the effects of panaxadiol saponins component （PDS-C） isolated from total saponins of panax ginseng on proliferation, differentiation and corresponding gone expression profile of megakaryoc...Objective： To investigate the effects of panaxadiol saponins component （PDS-C） isolated from total saponins of panax ginseng on proliferation, differentiation and corresponding gone expression profile of megakaryocytes. Methods： Bone marrow culture of colony forming assay of megakaryocytic progenitor cells （CFU-MK） was observed for the promoting proliferation mediated by PDS-C, and differentiation of megakaryocytic blasts caused by PDS-C was analyzed with flow cytometry in CHRF-288 and Meg-01 cells, as well as proliferation, differentiation-related genes expression profile and protein expression levels were detected by human gone expression microarray and western blot. Results： In response to PDS-C 10, 20 and 50 mg/L, CFU-MK from 10 human bone marrow samples was increased by 28.9± 2.7%, 41.0% ± 3.2% and 40.5% ± 2.6% over untreated control, respectively （P〈0.01, each）. Flow cytometry analysis showed that PDS-C treated CHRF-288 cells and Meg-01 cells significantly increased in CD42b, CD41, TSP and CD36 positive ratio, respectively. PDS-C induced 29 genes up-regulated more than two-fold commonly in both cells detected by human expression microarray representing 4000 known genes. The protein expression levels of ZNF91, c-Fos, BTF3a, GATA-1, RGS2, NDRG2 and RUNX1 were increased with western blot in correspond to microarray results. Conclusion： PDS-C as an effective component for hematopoiesis, play the role to enhance proliferation and differentiation of megakaryocytes, also up-regulated expression of proliferation, differentiation-related genes and proteins in vitro. KEYWORDS panaxadiol saponins, megakaryocyte, gone expression profile, proliferation, differentiation展开更多
Objective：To investigate the potential efficacy of panaxadiol saponins component（PDS-C）,a biologically active fraction isolated from total ginsenosides,to reverse chemotherapy-induced myelosuppression and pancytope...Objective：To investigate the potential efficacy of panaxadiol saponins component（PDS-C）,a biologically active fraction isolated from total ginsenosides,to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide（CTX）.Methods：Mice with myelosuppression induced by CTX were treated with PDS-C at a low-（20 mg/kg）,moderate-（40 mg/kg）,or high-dose（80 mg/kg） for 7 consecutive days.The level of peripheral white blood cell（WBC）,neutrophil（NEU） and platelet（PLT） were measured,the histopathology and colony formation were observed,the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot.Results：In response to PDS-C therapy,the peripheral WBC,NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner.Similarly,bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells（P〈0.01）.PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice,as evidenced by significantly increase in colony formation units-granulocytes/monocytes and-megakaryocytes（P〈0.01）.The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway,this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase（p-MEK） and extracellular signal-regulated kinases（p-ERK）,and receptor tyrosine kinase（C-kit） and globin transcription factor 1（GATA-1） in hematopoietic cells of CTX-treated mice（P〈0.05）.Conclusions：PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice,probably mediated by a mechanism involving MEK and ERK protein kinases,and C-kit and GATA-1 transcription factors.PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.展开更多
基金the National Natural Science Foundation of China(No 30370159)
文摘For making use of Ginseng resources that exhibit an antitumor activity and for finding new anticancer drugs, three new fatty acid ester compounds： 3/β-acetoxy panaxadiol （ Ⅰ ）, 3β-palmitic acid aceloxy panaxadiol （ Ⅱ ） , and 3β-octadecanoic acid aceloxy panaxadiol（ Ⅰ , Ⅱ, and m） were synthesized with panaxadiol, diacetyl oxide, palmityl chloride and stearyl chloride, and their structures were determined via MS, ^13C NMR, IR, TLC, and so on. The molar yields of the three compounds are 75.14%, 79. 08%, and 72. 57%, respectively. Meanwhile, the antitumor activity of the three new panaxadiol fatty acid ester derivatives and panaxadiol was compared by using the method of MTT. Tumor cell used was Vero cell line. Positive control was 5-FU, blank was an RPMI1640 culture medium, negative control was an RPMI1640 culture medium and the solvent for drugs to be tested. Compound Ⅰ has the strongest antitumor activity followed by panaxadiol; compounds Ⅱ and Ⅲ have similar and weakest antitumor activities. Furthermore, the antitumor activities of the panaxadiol fatty acid ester derivatives show positive correlation with the concentration of the test group, but show no relationship with the molecular weight of fatty acid. The methods that are used to synthesize the three compounds with high yields and strong antitumor activities are simple and show a great potential for meeting the needs of industrial manufacture of these drugs.
基金the National Natural Science Foundation of China for Distinguished Young Scholars(No.81025023)the National Natural Science Foundation of China(81202436)the West Light Foundation of the Chinese Academy of Sciences,and the Youth Innovation Promotion Association,CAS.
文摘28 Derivatives of panaxadiol(PD)and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells,of which 17 derivatives inhibited HBV DNA replication.Compounds 4,9,10,14,and 15 showed moderate activity against HBV DNA replication with IC50 values ranged from 7.27 to 28.21 lM compared with PD.In particular,3-O-20-thenoyl panaxadiol(4)inhibited not only HBV DNA replication(IC50=16.5 lM,SI[115.7)but also HBsAg(IC50=30.8 lM,SI[62.0)and HBeAg(IC50=18.2 lM,SI[105.14)secretions.Their structure–activity relationships were discussed for guiding future research toward the discovery of new anti-HBV agents.
基金Supported by Provincial Key Cultivation Laboratory for Digestive Disease Research,Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021SYS13,No.2020SYS13 and No.2021MX03.
文摘BACKGROUND Ulcerative colitis(UC),a chronic and challenging condition,necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications.Traditional Chinese medicine(TCM),known for its multi-stage and multi-targeted approach,has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment.Panax ginseng(P.ginseng),a commonly used remedy for UC in TCM,exemplifies this potential,although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated,highlighting the need for further research to unlock its full potential as a treatment option.AIM To investigate the key constituents and biological pathways through which P.ginseng exerts therapeutic effects on UC.METHODS Network pharmacology investigated the UC-alleviating mechanism of P.ginseng,including“active ingredient-target-disease”network analysis,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Panaxadiol(PD;active ingredient of P.ginseng)was tested in a mouse model of 3%dextran sulfate sodium-induced UC,with assessments of body weight,Disease Activity Index scores,and colon length.Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining,immunohistochemistry,real time-quantitative PCR,and western blotting.RESULTS By integrating and analyzing the targets of P.ginseng and UC,15 critical hub genes were discovered.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling.Among the 10 main active ingredients identified as potentially effective,PD was most abundant and was validated in vivo to mitigate weight loss,reduce Disease Activity Index scores,and prevent colon shortening.PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators.In addition,PD increased expression of mucin and tight junction proteins.Ultimately,PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK,while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.CONCLUSION PD alleviates colitis and aids intestinal barrier repair,partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways.These findings also suggest new research methods for treatment of UC with TCM.
基金Supported by National Natural Science Foundation of China(No.81373876)Zhejiang Provincial Natural Science Foundation(No.LY14H290004)Science and Technology Program of Zhejiang Province(No.2010C33098)
文摘Objective： To investigate the effects of panaxadiol saponins component （PDS-C） isolated from total saponins of panax ginseng on proliferation, differentiation and corresponding gone expression profile of megakaryocytes. Methods： Bone marrow culture of colony forming assay of megakaryocytic progenitor cells （CFU-MK） was observed for the promoting proliferation mediated by PDS-C, and differentiation of megakaryocytic blasts caused by PDS-C was analyzed with flow cytometry in CHRF-288 and Meg-01 cells, as well as proliferation, differentiation-related genes expression profile and protein expression levels were detected by human gone expression microarray and western blot. Results： In response to PDS-C 10, 20 and 50 mg/L, CFU-MK from 10 human bone marrow samples was increased by 28.9± 2.7%, 41.0% ± 3.2% and 40.5% ± 2.6% over untreated control, respectively （P〈0.01, each）. Flow cytometry analysis showed that PDS-C treated CHRF-288 cells and Meg-01 cells significantly increased in CD42b, CD41, TSP and CD36 positive ratio, respectively. PDS-C induced 29 genes up-regulated more than two-fold commonly in both cells detected by human expression microarray representing 4000 known genes. The protein expression levels of ZNF91, c-Fos, BTF3a, GATA-1, RGS2, NDRG2 and RUNX1 were increased with western blot in correspond to microarray results. Conclusion： PDS-C as an effective component for hematopoiesis, play the role to enhance proliferation and differentiation of megakaryocytes, also up-regulated expression of proliferation, differentiation-related genes and proteins in vitro. KEYWORDS panaxadiol saponins, megakaryocyte, gone expression profile, proliferation, differentiation
基金Supported by the Science and Technology Program Project of Zhejiang Province(No.2015C33173)Chinese Medicine Foundation of Young Talents in Zhejiang Province(No.2014ZQ006)Australia-China Institutional Links Research Program sponsored by the International Development Program of Education Australia(No.IDP 2-8)
文摘Objective：To investigate the potential efficacy of panaxadiol saponins component（PDS-C）,a biologically active fraction isolated from total ginsenosides,to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide（CTX）.Methods：Mice with myelosuppression induced by CTX were treated with PDS-C at a low-（20 mg/kg）,moderate-（40 mg/kg）,or high-dose（80 mg/kg） for 7 consecutive days.The level of peripheral white blood cell（WBC）,neutrophil（NEU） and platelet（PLT） were measured,the histopathology and colony formation were observed,the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot.Results：In response to PDS-C therapy,the peripheral WBC,NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner.Similarly,bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells（P〈0.01）.PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice,as evidenced by significantly increase in colony formation units-granulocytes/monocytes and-megakaryocytes（P〈0.01）.The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway,this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase（p-MEK） and extracellular signal-regulated kinases（p-ERK）,and receptor tyrosine kinase（C-kit） and globin transcription factor 1（GATA-1） in hematopoietic cells of CTX-treated mice（P〈0.05）.Conclusions：PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice,probably mediated by a mechanism involving MEK and ERK protein kinases,and C-kit and GATA-1 transcription factors.PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.
