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.

Clinical Study of Pai-Neng-Da Capsule(派能达胶囊) in the Treatment of Chronic Aplastic Anemia

Objective：To evaluate the efficacy and safety of Pai-Neng-Da Capsule（派能达胶囊t panaxadiol saponins component,PND）,a new Chinese patent medicine,on patients with chronic aplastic anemia（CAA）and to explore the optimal therapeutic regimen for CAA.Method：A total of 36 patients with CAA were enrolled and divided into three groups：the AP group（20 cases,andriol 120 mg/day ＋ PND 240 mg/day）,the ACP group（13 cases,andriol 120 mg/day ＋ cyclosporine 3-6 mg·kd（-1）·day（-1） ＋ PND 240 mg/day）,and the PND group（3cases,PND 240 mg/day）.All patients were treated and followed up for 6 months.Peripheral blood counts,renal and hepatic function and Chinese medical（CM） symptoms of patients were assessed and all indices were gathered at the beginning and end of the study.Result：In the AP group,no significant hematologic difference was observed at the end of 6-month treatment comparing with the beginning.In the ACP group,the blood counts were maintained at the same level after the 6-month treatment.In the PND group,trilineage hematologic improvement was displayed at the end of 6-month treatment comparing with the beginning.No significant difference was showed in renal and hepatic function in all patients.All patients＇ clinical symptom improved according to CM symptom score.The effective rates were 95%,73%and 100%,respectively.Conclusion：PND improved the efficacy and decreased side effects by cutting down the dosage of andriol,and it could also improve patients＇ clinical symptom and quality of life.PND were effective and safe in the treatment of CAA,it could be used alone or in combination with pharmacological agents such as andriol and cyclosporine.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule for Replacing Androgen Partially:A Clinical Multicenter Study

Objective:To evaluate the efficacy and safety of Pai-Neng-Da Capsule(panaxadiol saponins component,PNDC)in combination with the cyclosporine and androgen for patients with chronic aplastic anemia(CAA).Methods:A total of 79 CAA patients was randomly divided into 2 groups by a random number table,including PCA group[43 cases,orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d)plus andriol 80 mg/d]and CA group[36 cases,orally cyclosporine 5 mg/(kg·d)plus andriol 160 mg/d].All patients were treated and followed-up for 6 treatment courses over 24 weeks.The complete blood counts,score of Chinese medical(CM)symptoms were assessed and urine routine,electrocardiogram,hepatic and renal function were observed for safety evaluation.Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol.Results:The effective rates were 88.1%(37/42)in the PCA group and 77.8%(28/36)in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy.There was no significant difference in the white blood cell(WBC)counts,platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment.The masculinization score of female patient in the PCA group was significantly lower than the CA group(P<0.05).The mild abdominal distention was observed in 1 case in the PCA group.In CA group,the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case.Conclusion:The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization[Registried at Chinese Clinical Trial Registry(ChicTR1900028153)].