Pancytopenia （hemocytopenia） such as primary immune thrombocytopenia （ITP）, aplastic anemia and chronic neutropenia （agnogenic leukocytopenia） were often treated by glucocorticoids, androgen and immunosuppressiv...Pancytopenia （hemocytopenia） such as primary immune thrombocytopenia （ITP）, aplastic anemia and chronic neutropenia （agnogenic leukocytopenia） were often treated by glucocorticoids, androgen and immunosuppressive agents at present, but the response to these treatments has not been always satisfactory, and may cause serious adverse events. Our research has identified a biological active component in ginseng extract and the active component, panaxadiol saponins component （PDS-C）, was isolated from total saponins of ginsenosides, and formulated into capsules named as Painengda （派能达）. We successfully obtained approval from State Food and Drug Administration （SFDA） of China in 2010 to conduct clinical trials of PDS-C as class-five new Chinese patent medicine. Phase Ⅰand phase Ⅱ clinical trials of PDS-C and Painengda Capsule were carried out in the treatment of ITP and agnogenic leukocytopenia. Thecomposition and content of PDS-C have been analyzed and defined by high-performance liquid chromatography mass spectrometry （HPLC-MS） and HPLC using specific monomers of ginsenosides as the reference standards. PDS-C is very efficacious for treating mice and rats with ITP and aplastic anemia, and myelosuppression caused by chemotherapy or radiation. Our animal model studies and cell biology and molecular biology experiments demonstrated that PDS-C possessed dual activities, namely that of promoting proliferation and differentiation of hematopoietic progenitor cells, and that of regulating the immune function. PDS-C and Painengda Capsule as a new Chinese patent medicine have been successfully transferred to industry. We believe that PDS-C is effective and safe in the treatment of refractory hemocytopenia. The advantages are that it is effective in small doses, it is convenient to use because of its oral administration, its lack of adverse events, it could be used alone or in combination with pharmacological agents, which improve the efficacy and decrease adverse events.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
基金Supported by the National Natural Science Foundation of China (No.30271597)Australia-China Institutional Links Research Program by International Development Program of Education Australia(No.IDP 2-8)+1 种基金Science and Technology Foundation of Zhjiang Province,China(No.2004C23002)Natural Science Foundation of Zhjiang Province,China(No.ZD0007)
文摘Pancytopenia （hemocytopenia） such as primary immune thrombocytopenia （ITP）, aplastic anemia and chronic neutropenia （agnogenic leukocytopenia） were often treated by glucocorticoids, androgen and immunosuppressive agents at present, but the response to these treatments has not been always satisfactory, and may cause serious adverse events. Our research has identified a biological active component in ginseng extract and the active component, panaxadiol saponins component （PDS-C）, was isolated from total saponins of ginsenosides, and formulated into capsules named as Painengda （派能达）. We successfully obtained approval from State Food and Drug Administration （SFDA） of China in 2010 to conduct clinical trials of PDS-C as class-five new Chinese patent medicine. Phase Ⅰand phase Ⅱ clinical trials of PDS-C and Painengda Capsule were carried out in the treatment of ITP and agnogenic leukocytopenia. Thecomposition and content of PDS-C have been analyzed and defined by high-performance liquid chromatography mass spectrometry （HPLC-MS） and HPLC using specific monomers of ginsenosides as the reference standards. PDS-C is very efficacious for treating mice and rats with ITP and aplastic anemia, and myelosuppression caused by chemotherapy or radiation. Our animal model studies and cell biology and molecular biology experiments demonstrated that PDS-C possessed dual activities, namely that of promoting proliferation and differentiation of hematopoietic progenitor cells, and that of regulating the immune function. PDS-C and Painengda Capsule as a new Chinese patent medicine have been successfully transferred to industry. We believe that PDS-C is effective and safe in the treatment of refractory hemocytopenia. The advantages are that it is effective in small doses, it is convenient to use because of its oral administration, its lack of adverse events, it could be used alone or in combination with pharmacological agents, which improve the efficacy and decrease adverse events.
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
