title: Artemisiae capillaris herba induces prolonged survival of fully cardiac allografts and generates regulatory cells in mice.
abstract: Inchingorei-san (TJ-117), a 6-component herbal medicine, is used in Japan for the treatment of vomiting, urticaria, and liver and kidney disorders with few side effects. In this study we investigated the effect of TJ-117 on alloimmune responses in murine cardiac allograft transplantation. CBA (H2(k)) mice underwent transplantation of a C57BL/6 (B6, H2(b)) heart with oral administration of TJ-117 (or 1 component of TJ-117) from the day of transplantation for 7 days. CBA recipients given 1 g/kg/d of TJ-117 showed prolonged B6 allograft survival (median survival time [MST], 23 days). Naive CBA mice rejected B6 cardiac grafts acutely (MST, 7 days). Moreover, Artemisiae capillaris herba (ACH; 1g/kg/d) 1 component of TJ-117, significantly prolonged B6 allograft survival (MST, > 100 days). However, the other 5 components of TJ-117 were individually less effective than TJ-117 or ACH. ACH also suppressed splenocyte proliferation and interferon-γ production. Secondary CBA recipient showed prolonged survival of B6 hearts after treatments with whole splenocytes from primary ACH-treated CBA recipients carrying B6 cardiac allografts for 30 days (MST, >50 days). Flow cytometry studies showed increased CD4(+)CD25(+)Foxp3(+) regulatory cells in transplant recipients given ACH. In conclusion, ACH, 1 component of TJ-117, as well as TJ-117 induced hyporesponsiveness to fully allogeneic cardiac allografts with generation of CD4(+)CD25(+)Foxp3(+) regulatory cells.
authors.affiliation: Department of Surgery, Teikyo University, Tokyo, Japan.
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.forename: M
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Niimi
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D019306:Artemisia; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D006648:Histocompatibility; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D013997:Time Factors
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D007155:Immunologic Factors; D053645:Interleukin-2 Receptor alpha Subunit; D010936:Plant Extracts; D007371:Interferon-gamma