Inchingorei-san (TJ-117) and Artemisiae Capillaris Herba Induced Prolonged Survival of Fully Mismatched Cardiac Allografts and Generated Regulatory Cells in Mice

Abstract

We investigated Inchingorei-san (TJ-117), a 6-component Japanese herbal medicine, on alloimmune responses in murine cardiac allograft transplantation. CBA mice underwent transplantation of a C57BL/6 (B6) heart and received oral administration of TJ-117 or each component of TJ-117 from the day of transplantation until 7 days afterward. Naive CBA mice rejected B6 cardiac grafts acutely (median survival time (MST), 7 days). CBA recipients given 1 g/kg/day of TJ-117 had prolonged B6 allograft survival (MST, 37 days). Moreover, given 1 g/kg/day of Artemisiae Capillaris Herba (ACH), one component of TJ-117, indefinitely prolonged B6 allograft survival (MST, >100 days). However, other five components of TJ-117 were less effective than TJ-117 and ACH. Secondary CBA recipients given whole splenocytes, CD4+, and CD4+CD25+ cells from primary ACH-treated CBA recipients with B6 cardiac allografts 30 days after grafting had prolonged survival of B6 hearts (MSTs, 57, >100, and >100 days, resp.). Flow cytometry studies showed that the CD4+CD25+Foxp3+ regulatory cell population was increased in transplant recipients given ACH. Cell proliferation, interleukin-2, and interferon-γ were suppressed in ACH-treated mice, whereas interleukin-4 and interleukin-10 were upregulated. In conclusion, ACH, one component of TJ-117, as well as TJ-117 induced hyporesponsiveness to fully allogeneic cardiac allografts and may generate CD4+CD25+Foxp3+ regulatory cells.

Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival

“…Proliferation was assessed by using an Enzyme-linked Immunosorbent Assays (ELISA) for bromodeoxyuridine incorporation (Biotrak, version 2, Amersham, Little Chalfont, United Kingdom [UK]) according to the manufacturer’s instructions. MLC studies were performed as described previously [ 25 ].…”

“…Enzyme-linked immunoabsorbent assays (ELISAs) were performed as described previously [ 25 ] to assess plasma levels of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-γ in the supernatant of the MLC on day 4.…”

“…Li and Weir [ 22 ] showed that Radix Tripterygium wilfordii, a Chinese herbal medicine, has immunosuppressive effects in human blood mononuclear cells in vitro. In recent studies in our murine model, oral administration of the Japanese herbal medicines Sairei-to (TJ-114) [ 23 ], Tokishakuyaku-san (TJ-23) [ 24 ], or Artemisiae Capillaris Herba [ 25 ] was associated with significantly prolonged survival of allogeneic cardiac grafts and generation of regulatory cells. In the current study, we examined whether olfactory exposure to TJ-23 affected duration of allograft survival in the same model.…”

Induction of Regulatory T Cells and Prolongation of Fully Allogeneic Cardiac Grafts by Herbal Medicine, Shohangekabukuryo-to

“…For example, Mao-to (TJ-27) has been used to treat influenza infection [6], Dai-bofu-to (TJ-97) has been used to treat rheumatoid arthritis [7]. In recent studies of our murine model, oral administration of the herbal medicines Tokishakuyaku-san (TJ-23) [8], Sairei-to (TJ-114) [9], or Artemisiae Capillaris Herba [10] was associated with significantly prolonged survival of allogeneic cardiac grafts (median survival times (MSTs) of all groups >100 days) and generation of regulatory cells. Based on these findings, we wondered if there were other several herbal medicines could also affect the immune response.…”

Combination of Paeoniae Radix and Cnidii Rhizoma Prolonged Survival of Fully Mismatched Cardiac Allografts and Generated Regulatory Cells in Mice

“…Since Japanese government health officials officially recognized the therapeutic effects of Japanese herbal (Kampo) medicines about 30 years ago, these medicines have been widely used as alternative therapy for several diseases. In recent studies of our murine model, oral administration of the Japanese herbal medicines Tokishakuyakusan (TJ-23) [ 1 ], Saireito (TJ-114) [ 2 ], or Artemisiae Capillaris Herba [ 3 ] was associated with significantly prolonged survival of allogeneic cardiac grafts (median survival times (MSTs) of all groups > 100 days) and generation of regulatory cells. Paeoniae radix ( Paeonia lactiflora ) and Cnidii rhizoma ( Cnidium officinale ) were two components of TJ-23, and, in this study, we examined whether the combination of Paeoniae radix and Cnidii rhizoma could affect the duration of allograft survival in the same model.…”