The Liquid Culture Filtrates of Entomogenous fungus Paecilomyces tenuipes and Its Glycoprotein Constituent Protects against Anemia in Mice Treated with 5-Fluorouracil(Pharmacognosy)

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概要

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• The purpose of the present study was to investigate the efficacy of a liquid culture filtrates of the entomogenous fungus Paecilomyces tenuipes (PTCF) and its main active glycoprotein-enriched (PGF) fraction against hematotoxicity in mice treated with 5-fluorouracil (5-FU). Oral administration of PTCF (100 mg/kg/d) for 7 consecutive days after 5-FU injection significantly suppressed reductions in the red and white blood cell counts in peripheral blood, and accelerated their recoveries. From PTCF, glycoprotein-enriched fraction (PGF, >90% protein, approximately 15 kDa determined by SDS-PAGE) was separated as active ingredient that ameliorates 5-FU-induced anemia. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of trypsinized-PGF showed 11 fragment ion peaks. Effective recoveries of erythrocytopenia and leukocytopenia were observed when PGF was co-administered with murine recombinant erythropoietin (mrEPO; 5U/mouse). Oral administration of PGF also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 12, and markedly hastened their recoveries on day 20, in dose-dependent manners. Reductions in erythroid progenitor colonies, such as colony-forming units (CFU)-erythroid and burst-forming units-erythroid mix, formed by bone marrow cells from 5-FU-treated mice were markedly improved by oral administration of PGF with subcutaneous mrEPO. Oral administration of PGF also increased the myeloid lineage progenitor, CFU-granulocyte-macrophages, in cultured bone marrow cells. These findings suggest that PGF isolated from P. tenuipes has the potential to protect against 5-FU-inudced erythrocytopenia and leukopenia, especially in combination with mrEPO, and also has hematopoietic activity, through stimulation of immature erythroid as well as myeloid progenitor cell differentiation.

• 公益社団法人日本薬学会の論文
• 2008-08-01

著者

• TOMOSUGI Naohisa

  Division of Advanced Medicine, Medical Research Institute, Kanazawa Medical University

• ISHIGAKI Yasuhito

  Division of Core Facility of Medical Research Institute, Kanazawa Medical University

• TAKANO Fumihide

  Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science an

• TAKATA Takanobu

  Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science an

• Tatsuno Takanori

  Dep. Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Sci. And Technol.

• Ishigaki Yasuhito

  Div. Of Core Facility Medical Res. Inst. Kanazawa Medical Univ.

• Ishigaki Yasuhito

  金沢大学 自然科学研究科天然物化学

• Ishigaki Yasuhito

  Division Of Core Facility Medical Research Institute Kanazawa Medical University

• Takano Fumihide

  Dep. Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Sci. And Technol.

• Takano Fumihide

  Kanazawa Univ. Kanazawa Jpn

• OHTA Tomihisa

  Kanazawa University

• TANAKA TOMOAKI

  Department of Clinical Endocrinology and Metabolism, Chiba University Hospital

• Yahagi Nobuo

  Department Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Science And

• Yahagi Remiko

  Department Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Science And

• TSUCHIDA Hideyuki

  Division of Core Facility Medical Research Institute, Division of Molecular Oncology and Virology, K

• FUSHIYA Shinji

  Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University

• OHTA Tomihisa

  Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science an

• Ohta Tomihisa

  Kanazawa Univ. Kanazawa Jpn

• Ohta Tomihisa

  Department Of Applied Chemistry And Biotechnology Faculty Of Engineering Fukui University

• Tomosugi Naohisa

  Division Of Advanced Medicine Medical Research Institute Kanazawa Medical University

• Tomosugi Naohisa

  Mcprot Biotechnology Co. Ltd.

• Ohta Tomihisa

  Dep. Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Sci. And Technol.

• Tanaka Tomoaki

  Department Of Clinical Endocrinology And Metabolism Chiba University Hospital

• Fushiya S

  Department Of Kampo Pharmaceutical Sciences Nihon Pharmaceutical University

• Fushiya Shinji

  Department Of Kampo Pharmaceutical Sciences Nihon Pharmaceutical University

• Takano Fumihide

  Department Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Science And

• Tanaka Tomoaki

  Department Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Science And

• Tanaka Tomoaki

  Department Of Agricultural Chemistry Faculty Of Agriculture Tohoku University:basic Research Laborat

• Tsuchida Hideyuki

  Division Of Core Facility Medical Research Institute Division Of Molecular Oncology And Virology Kan

• Takata Takanobu

  Division Of Molecular Oncology And Virology Medical Research Institute Kanazawa Medical University

• Nakaya Naoki

  Department Of Medical Oncology Kanazawa Medical University

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