Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model

Journal of Immunology Research, Aug 2017

A derivative formula, DGBX, which is composed of three herbs (Radix astragali, Radix Angelicae sinensis, and Coptis chinensis Franch), is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT) (Radix astragali and Radix Angelicae sinensis). We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs) due to the aberrant immune response in a mouse model of aplastic anemia (AA). Cyclosporine (CsA), an immunosuppressor, was used as the positive control. Our results indicated that DGBX could downregulate the production of IFNγ in bone marrow cells by interfering with the binding between SLAM and SAP and the expressions of Fyn and T-bet. This herbal formula can also inhibit the activation of Fas-mediated apoptosis, interferon regulatory factor-1-induced JAK/Stat, and eukaryotic initiation factor 2 signaling pathways and thereby induce proliferation and attenuate apoptosis of HSCs. In conclusion, DGBX can relieve the immune-mediated destruction of HSCs, repair hematopoietic failure, and recover the hematopoietic function of HSCs in hematogenesis. Therefore, DGBX can be used in traditional medicine against AA as a complementary and alternative immunosuppressive therapeutic formula.

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Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model

Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model Jingwei Zhou,1,2 Xue Li,1 Peiying Deng,1 Yi Wei,1 Juan Liu,1 Meng Chen,3 Yamei Xu,4 Dongmei Zhang,1 Lingqun Zhu,1 Lixia Lou,1 Bin Dong,1 Qiushuo Jin,1 and Limin Chai1 1Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China 2Department of Rheumatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China 3School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China 4Department of Hematology & Oncology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China Correspondence should be addressed to Limin Chai; moc.liamtoh@iahcnimil Received 9 January 2017; Revised 1 June 2017; Accepted 12 July 2017; Published 16 August 2017 Academic Editor: Qingdong Guan Copyright © 2017 Jingwei Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract A derivative formula, DGBX, which is composed of three herbs (Radix astragali, Radix Angelicae sinensis, and Coptis chinensis Franch), is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT) (Radix astragali and Radix Angelicae sinensis). We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs) due to the aberrant immune response in a mouse model of aplastic anemia (AA). Cyclosporine (CsA), an immunosuppressor, was used as the positive control. Our results indicated that DGBX could downregulate the production of IFNγ in bone marrow cells by interfering with the binding between SLAM and SAP and the expressions of Fyn and T-bet. This herbal formula can also inhibit the activation of Fas-mediated apoptosis, interferon regulatory factor-1-induced JAK/Stat, and eukaryotic initiation factor 2 signaling pathways and thereby induce proliferation and attenuate apoptosis of HSCs. In conclusion, DGBX can relieve the immune-mediated destruction of HSCs, repair hematopoietic failure, and recover the hematopoietic function of HSCs in hematogenesis. Therefore, DGBX can be used in traditional medicine against AA as a complementary and alternative immunosuppressive therapeutic formula. 1. Introduction Aplastic anemia (AA) is a rare acquired bone marrow failure syndrome resulting from immune-mediated destruction of hematopoietic stem cells (HSCs), caused largely by many quantitative and qualitative defects in HSCs [1]. Allogeneic stem cell transplant can cure severe AA. Nevertheless, transplantation in patients who are old or lack family donors has many challenges [2]. The molecular basis of the aberrant immune response and deficiencies in HSC is now being defined genetically. Immunosuppression by antithymocyte globulins and cyclosporine A (CsA) is effective on restoring blood cell production in the majority of AA patients. However, the incidence of relapse and evolution of clonal hematological diseases remain high [3]. Danggui Buxue Tang (DBT), one of the simplest traditional Chinese medicine (TCM) decoctions, has been used in the treatment of blood deficiency syndrome for more than 800 years in China. DBT is composed of two herbs, Radix astragali (Milkvetch Root) and Radix Angelicae sinensis (Chinese Angelica), boiled together at a 5 : 1 ratio. Pharmacological studies indicated that DBT has effects on bone development [4], blood enhancement [5], and immune stimulation [6]. Several studies have verified the hematopoietic function of DBT in a mouse model of bone marrow suppression. It can increase the production of peripheral blood and nucleated bone marrow cells (BMCs) and the colony count of hematopoietic stem/progenitor cells (HSPCs) in vitro; regulate the expression of cytokines, such as erythropoietin, thrombopoietin, and granulocyte-macrophage colony-stimulating factor in bone marrow microenvironment; and contribute to cell cycle of HSPCs [7]. For the bone marrow failure syndrome resulting from immune-mediated destruction of HSC, we modified DBT to prepare a derivative herb formula (DGBX) by adding Coptis chinensis Franch (Coptidis rhizoma) for reinforcing the regulatory effect on aberrant immune response in the bone marrow of patients with AA. Pharmacological studies validated that Coptis chinensis Franch modulates immune responses and controls certain inflammation-related diseases [8]. The combination of these three herbs can contribute to multitargeting, multichannel immunosuppressive effects in AA treatment. We investigated the possible mechanisms underlying the immunosuppressive and hematopoietic functions of DGBX in an immune-mediated AA mouse model. Cs (...truncated)


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Jingwei Zhou, Xue Li, Peiying Deng, Yi Wei, Juan Liu, Meng Chen, Yamei Xu, Dongmei Zhang, Lingqun Zhu, Lixia Lou, Bin Dong, Qiushuo Jin, Limin Chai. Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model, Journal of Immunology Research, 2017, 2017, DOI: 10.1155/2017/9786972