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Radioprotective effect of Immunomodulator Ginsan. Yun Yeon-Sook Radiological and Medical Sciences Research Center KIRAMS , Seoul, Korea. Acute Radiation Syndromes in Man after Whole-Body Irradiation. Granulocytes Platelets Erythrocytes Lymphocytes. 100. 80. 60.
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Radioprotective effect of Immunomodulator Ginsan Yun Yeon-Sook Radiological and Medical Sciences Research Center KIRAMS, Seoul, Korea
Acute Radiation Syndromes in Man after Whole-Body Irradiation
Granulocytes Platelets Erythrocytes Lymphocytes 100 80 60 Normalized to pre-irradiation value (%) 40 20 0 0 5 25 10 15 20 Time (Days) Peripheral blood counts of rats following 500cGy whole-body irradiation (Casarett, 1968)
We screened radioprotective immunostimulators from 70 medicinal plants which have been used in chinese medicine.
Polysaccharide composed with a(1 6)-Glucopyranoside and b(2 6)-Fructofuranoside Ginseng Polysaccharide : Gins + -an O O O H H O C H C H H O 2 2 H H O H O H H O H H O H O O H O H H C H C H O O H H 2 2 O H H H O H H O H O H O H O H H O O C H C H O O H H 2 2 H H O H H O H H H O H O H O H H O O H H O H Ginsan
75 50 No. of colonies /1 x 105 BM cells 25 0 control rad 100 200 dose of Ginsan (mg/kg) Effect of Ginsan on the formation of GM-CFU 5 days after sublethal irradiation
Effect of Ginsan on the Peripheral blood hematology of mice 9 days after irradiation
100 90 80 LD50/30 =10.76 Ginsan treated 70 60 Percent Survival at 30 Days 50 40 LD50/30 =7.46 PBS treated 30 20 10 0 0 2 4 6 8 10 12 14 Radiation dose(Gy) Survival enhancing effect of Ginsan - Measurement of DRF (dose reducing factor)
Antisepticemic activity of Ginsan on the S. aureus peritoneal sepsis challenge intraveneous injection oral intubation Percent of survival Percent of survival Dose of Ginsan(mg/kg) Dose of Ginsan(mg/kg)
Effect of Ginsan treatment on lung consolidation scores in influenza A(H3N2) virus-infected mice 4 J H N H * J B 3 N Ginsan (200mg/kg)x4 B Ginsan (100mg/kg) x4 J Ginsan (50mg/kg) x4 H * 2 J B Ribavirin (75mg/kg) x10 F H Mean Lung Score B Saline N N 1 * F *P<0.05 * * 0 ? F H J B F F 0 3 6 9 Days Post-Virus Exposure
Anticancer Immunostimulatory activity
Ct Ginsan 3 6 24h 3 6 24h 60 TNF- 50 GM-CSF SC Ginsan 40 IL-12 OK432 IL-1 30 % cytotoxicity lentinan IFN- 20 IL-2 10 IL-4 IL-5 0 IL-10 10 :1 30 :1 100 :1 -actin E/T ratio Generation of activated killer cells and increase of cytokine production by Ginsan
Inhibitory effect of Ginsan on the experimental metastasis of B16-F10 melanoma PBS-control Inhibition of B16-F10 melanoma Agents counts % inhibition - 44.2 Ginsan 533 278 PBS Ginsan
Action Mechanism of Ginsan Ginsan Ginsan Hematopoisis Macrophage B cell • Generation and/or • differentiation of SC • Cytokine production IL-6 GM-CSF IFNg Cell expansion IL-1 IL-12 IL-15 IFNg BM NK cell T cell IL-3 IL-6 IL-2 IFNg Blastogenesis Mono/Gra AK cell Lym Plt RBC TNFa NO/O2- Antitumor effect Bactericidal effect Tumor • Mitogenic activity • Killer cell generation • Cytokine production MRSA, VRSA (Due to macrophage-derived toxic material production)