The Korea Journal of Herbology (대한본초학회지)

The Korea Association of Herbology (대한본초학회)
권호 표지
DOI QR코드

DOI QR Code

Studies on the regulation of Hematopoietic enhancement of Brassica campestris var narinosa., Canavalia gladiata DC semen and their combinational prescription via Jak2/STAT5/GATA1 Pathway in Sca-1+ hematopoietic stem cells

Sca-1+골수조혈세포에서 JAK2/STAT5/GATA-1 신호전달 경로를 통한 다채, 도두 그리고 두 조합물에 의한 조혈증진 조절에 관한 연구

  • Kim, Kunhoae (Central Research Laboratories of Aekyung industrial Co. Ltd.) ;
  • Kim, Seung-Hyung (Institute of Traditional Medicine and Bioscience, Daejeon University) ;
  • Cho, In-Sik (Central Research Laboratories of Aekyung industrial Co. Ltd.) ;
  • Kim, Han-Young (Central Research Laboratories of Aekyung industrial Co. Ltd.) ;
  • Kim, Dong-Seon (Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine) ;
  • Lee, Young-Cheol (Department of Herbology, College of Oriental Medicine, Sangji University)
  • Received : 2013.06.19
  • Accepted : 2013.07.20
  • Published : 2013.07.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Brassica campestris var narinosa (BCN), Canavalia gladiata DC semen (CGD) and their combinational prescription (BCN+CGD) have been use to demonstrate to regulate hematopoiesis. In the current study, we investigated whether Brassica campestris var narinosa, Canavalia gladiata DC semen and their combinational prescription is related to hemato-potentiating function using Sca-$1^+$ hematopoietic stem cells (Sca-$1^+HSCs$) as a testing system. Methods : Sca-$1^+HSCs$ isolated from femur in C57bl/6 mice with leukopenia and thrombocytopenia induced by cyclophosphamide (CTX). Then, Real-time PCR was performed to measure the mRNA expression, ELISA and haematopoiesis-related gene (EPO, TPO, IL-3, SCF, c-kit, GM-CSF), the phosphorylation of JAK2, GATA-1 and STAT-5a/b were observed by western blot, and the numbers of $CD117^+/Sca-1^+$ cell and the number of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E), semisolid clonogenic assay was performed. Result : When Sca-$1^+HSCs$ were treated with Brassica campestris var narinosa, Canavalia gladiata DC semen and their combinational prescription with rIL-3/rSCF, the expression of haematopoiesis-related (EPO, TPO, IL-3, SCF, c-kit, and GM-CSF) were significantly increased at the levels of mRNA as well as production in Sca-$1^+HSCs$. Additionally, CGS enhanced phosphorylation of JAK2, GATA-1, and signal transducer and activator of transcription-5a/b (STAT-5a/b) in Sca-$1^+HSCs$. Furthermore, their combinational prescription (BCN+CGD) significantly enhanced the growth rate of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E) in vitro. Conclusion : These result suggest that Brassica campestris var narinosa (BCN) and Canavalia gladiata DC have hematopoietic enhancement via hematopoietic cytokine-mediated JAK2/GATA-1/STAT-5a/b pathway, and their combinational prescription (BCN+CGD) has superior hematopoietic enhancement to those of individual extracts.

Keywords

References

  1. Torino F, Barnabei A, Paragliola RM, Baldelli R, Appetecchia M, Corsello SM. Thyroid as unintended side effect of anticancer drugs. Thyroid. 2013 ; 1 : 1-5.
  2. Slovak ML, Bedell V, Lew D et al. Screening for clonal hematopoiesis as a predictive marker for development of therapy-related myeloid neoplasia (t-MN) following neoadjuvant therapy for breast cancer: a Southwest Oncology Group study (S0012). Breast Cancer Res Treat. 2010 ; 119 : 391-8. https://doi.org/10.1007/s10549-009-0597-5
  3. Gordon MY, Clarke D, Atkinson J, Greaves MF. Hemopoietic progenitor cell binding to the stromal microenvironment in vitro. Exp Hemtol. 1990 ; 18(7) : 837-42.
  4. Allen TD, Dexter TM. The essential cells of the hematopoietic microenvironment. Exp Hematol. 1984 ; 12(7) : 517-21.
  5. Halsey C, Tunstall O, Gibson B, Roberts I, Graham G. Role of GATA-1s in early hematopoiesis and differences between alternative splicing in human and murine GATA-1. Blood. 2010 ; 22(115) : 3415-6.
  6. Grass JA, Boyer ME, Pal S, Wu J, Weiss MJ, Bresnick EH. GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling. PNAS . 2003 ; 22 : 8811-6.
  7. Nosaka T, Kitamura T. Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) in hematopoietic cells. Int J Hematol. 2000 ; 71 : 309-19.
  8. Tani A, Kiyota M, Aiga I. Trace gases generated in closed plant cultivation systems and their effects on plant growth. Biol Sci Space. 1995 ; 9(4) : 314-26. https://doi.org/10.2187/bss.9.314
  9. Li S. Compendium of Materia Medica. Beijing : Foreign Languages Press. 2003 ; 24 : 874.
  10. Jeon KS, Na HJ, Kim YM, Kwon HJ. Antiangiogenic activity of 4-O-methylgallic acid from Canavalia gladiata, a dietary legume. Biochem Biophys Res Commun. 2005 ; 20(4) : 1268-74.
  11. Ekanayake S, Skog K, Asp NG. Canavanine content in sword beans (Canavalia gladiata): Analysis and effect of processing. Food Chem Toxicol. 2007 ; 45 : 797–803. https://doi.org/10.1016/j.fct.2006.10.030
  12. Yoshida H, Yoshida N, Kuriyama I, Tomiyama-Sakamoto Y, Mizushina Y. Profiles of lipid components, fatty acid distributions of triacylglycerols and phospholipids in Jack beans (Canavalia gladiata DC.). Food Chem. 2013 ; 136(2) : 807-12. https://doi.org/10.1016/j.foodchem.2012.08.087
  13. Kim KA. Screening of Antioxidants from Canavalia gladiata DC. Master program in Department of food Engineering Graduate School Of KonKuk University. 2000 ; 22 : 7-13.
  14. Pugalenthi M, Doss A, Rajendrakumaran D, Vadivel V. Antibacterial activity of Canavalia ensiformis L.DC seeds due to solvent extract and fraction method. Indian J Sci Technol. 2010 ; 3(1) : 94-5.
  15. Nimenibo-Uadia R. Effect of aqueous extract of Canavalia ensiformis seeds on hyperlipidaemia and hyperketonaemia in alloxan-induced diabetic rats. BIOKEMISTRI. 2003 ; 15(1) : 7-15.
  16. Wen LY, Bae SM, Chun HJ, Park KS, Ahn WS. Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells. Lasers Med Sci. 2012 ; 27(2) : 445-52. https://doi.org/10.1007/s10103-011-0950-x
  17. Guest I, Uetrecht J. Bone marrow stem cell protection from chemotherapy by low-molecular-weight compounds. Exp Hematol. 2001 ; 29(2) : 123-37. https://doi.org/10.1016/S0301-472X(00)00621-4
  18. Isern J, Martin-Antonio B, Ghazanfari R, Martin AM, Lopez JA, Del Toro R, Sanchez-Aguilera A, Arranz L, Martin-Perez D, Suarez-Lledo M, Marin P, Van Pel M, Fibbe WE, Vazquez J, Scheding S, Urbano-Ispizua A, Mendez-Ferrer S. Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion. Cell Rep. 2013 ; 3(5) : 1714-24. https://doi.org/10.1016/j.celrep.2013.03.041
  19. Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of hemopoietic stem cells in vitro. J Cell Physiol. 1977 ; 91 : 335-44. https://doi.org/10.1002/jcp.1040910303
  20. Verfaillie CM, McCarthy JB, McGlave PB. Differentiation of primitive human multipotent hematopoietic progenitors is accompanied by alterations in their interaction with fibronectin. J Exp Med. 1991 ; 174(3) : 693-703. https://doi.org/10.1084/jem.174.3.693
  21. Hardy CL, Tavassoli M. Homing of hemopoietic stem cells to hemopoietic stroma. Adv Exp Med Biol. 1988 ; 241 : 129-33.
  22. Thalmeier K, Meisner P, Reisbach G, Hültner L, Mortensen BT, Brechtel A, Oostendorp RA, Dormer P. Constitutive and modulated cytokine expression in two permanent human bone marrow stromal cell lines. Exp Hematol. 1996 ; 24(1) : 1-10.
  23. Brugger W, Mocklin W, Heimfeld S, Berenson RJ, Mertelsmann R, Kanz L. Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin-$1\beta$(IL-$1\beta$), IL-6, IL-3, interferon-$\gamma$, and erythropoietin. Blood. 1993 ; 81(10) : 2579-84.
  24. Gabbianelli M, Pelosi E, Montesoro E, Valtieri M, Luchetti L, Samoggia P, Vitelli L, Barberi T, Testa U, Lyman S, Peschle C. Multi-level effects of flt3 ligand on human hematopoiesis: expansion of putative stem cells and proliferation of granulomonocyte progenitors/monocytic precursors. Blood. 1995 ; 86(5) : 1661-70.
  25. Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 ; 264(5164) : 1415-21. https://doi.org/10.1126/science.8197455
  26. Pal S, Cantor AB, Johnson KD, Moran TB, Boyer ME, Orkin SH, Bresnick EH. Coregulator-dependent facilitation of chromatin occupancy by GATA-1. PNAS. 2004 ; 101(4) : 980-5. https://doi.org/10.1073/pnas.0307612100
  27. Gregory T, Yu C, Ma A, Orkin SH, Blobel GA, Weiss MJ. GATA-1 and Erythropoietin Cooperate to Promote Erythroid Cell Survival by Regulating bcl-xL Expression. Blood. 1999 ; 94(1) : 87-96.
  28. Zhao W, Kitidis C, Fleming MD, Lodish HF, Ghaffari S.Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway. Blood. 2006 ; 107(3) : 907–15.