Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice.

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice. METHODS: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot. RESULTS: The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3+ and CD3+CD4+ cells and reduced CD3+CD8+ cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4+CD25+FoxP3+ cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05). CONCLUSION: PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.

Ginseng-Derived Panaxadiol Saponins Promote Hematopoiesis Recovery in Cyclophosphamide-Induced Myelosuppressive Mice: Potential Novel Treatment of Chemotherapy-Induced Cytopenias.

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.

Research and development of the effective components of panaxdiol saponin as new Chinese patent medicine for treating hemocytopenia.

Pancytopenia (hemocytopenia) such as pr imary immune primary thrombocytopenia (ITP), aplastic anemia and chronic neutropenia (agnogenic leukocytopenia) were of ten t reated by glucocor t icoids, androgen and often treated glucocorticoids, 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. 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 I and phase II clinical trials of PDS-C and Painengda Capsule were carried out in the treatment of ITP and agnogenic leukocytopenia. The composition and content of PDS-C have been analyzed and defined by high-performance liquid chromatography-chromatographymass spectrometry (HPLC-MS) and HPLC using specific monomers of ginsenosides as the reference standards. mass 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.

Serum thromboxane B2 compared to five other platelet function tests for the evaluation of aspirin effect in stable cardiovascular disease.

BACKGROUND: To assess the role of serum thromboxane B(2) (TXB(2)) measurements and the correlation between platelet function studies, in patients with stable cardiovascular disease on aspirin or clopidogrel. METHODS: 76 patients (47 on aspirin, 16 clopidogrel, 13 both) underwent assessment of TXB(2), whole blood aggregometry (WBA) after stimulation with (i) arachidonic acid (0.5mM), (ii) ADP (5 microM), (iii) collagen (1 and 5 microg/ml), PFA-100, and Cone and Plate Analyzer. Clopidogrel patients were additionally assessed by the VerifyNow System. RESULTS: TXB(2) values ranged between 0.2 and 56.2 ng/ml, with significant separation between those taking aspirin, clopidogrel and controls (0.45 ng/ml vs 6.85 ng/ml vs 12.97 ng/ml, p<0.001). There was moderate correlation between WBA-AA and TXB(2) (r=0.487, p<0.001), PFA-100((R)) (r=0.599, p<0.001), WBA-Col1 (r=0.424, p<0.001), WBA-Col1:5 (r=0.417, p<0.001), and between TXB(2) and PFA-100((R)) (r=0.509, p<0.001). The prevalence of aspirin non-responders for WBA-AA, TXB(2), PFA-100((R)), CPA and Coll1:5 was 13.1%, 8.2%, 14.8%, 9.7% and 16.4% respectively. Individual patients were not consistently classified as aspirin non-responders in all tests. Those with inadequate aspirin response on > or =3 tests had higher TXB(2) levels (mean 1.57+/-1.66, range 0.553-4.45 vs mean 0.45+/-0.18, range 0.23-1.50) (p=0.001). Clopidogrel suppressed TXB(2) (p=0.02), WBA-AA (p<0.001), WBA-Col1 (p=0.012) and WBA-ADP (p<0.001) compared to controls. TXB(2) in patients ingesting fish oil tablets was lower compared to those without (0.4 ng/ml vs 0.52 ng/ml, p=0.004). Obesity was associated with higher TXB(2) values (0.61 vs 0.41, p=0.01). CONCLUSION: Serum TXB(2) measurements are a direct measure of the pharmacological effect of aspirin, are easily performed and correlate with other measures of platelet function. Serum TXB(2) measurements could be a useful sole measure of aspirin non-response, and may be even more predictive when performed in tandem with a global measure of platelet function. Aspirin and clopidogrel both suppressed several platelet pathways.