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Open Access Open Badges Research article

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

Xiangyuan Jin12, Masateru Uchiyama13, Qi Zhang14 and Masanori Niimi1*

Author Affiliations

1 Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan

2 Department of Thoracic and Cardiovascular Surgery, the 4th Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin, Heilongjiang Province 150001, China

3 Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan

4 Department of Dermatology, Huashan Hospital, Fudan University, Urumqi Road 12, Shanghai, China

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Journal of Cardiothoracic Surgery 2014, 9:82  doi:10.1186/1749-8090-9-82

Published: 9 May 2014



Herbal medicines have unique odors, and the act of smelling may have modulatory effects on the immune system. We investigated the effect of olfactory exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune responses in a murine model of cardiac allograft transplantation.


Naïve or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart and were exposed to the odor of TJ-23 until rejection. Some naïve CBA recipients of an allograft were given olfactory exposure to Sairei-to (TJ-114), trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation lacking one component. Adoptive transfer studies were performed to determine whether regulatory cells were generated.


Untreated CBA mice rejected their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure to TJ-23 had significantly prolonged allograft survival, whereas those exposed to the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did not. Secondary allograft recipients that were given, at 30 days after transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from primary recipients exposed to the odor of TJ-23 had indefinitely prolonged allograft survival.


Prolonged survival of cardiac allografts and generation of regulatory cells was associated with exposure to the odor of TJ-23 in our model. The olfactory area of the brain may have a role in the modulation of immune responses.

Odor; Tokishakuyaku-san; Heart transplantation; Regulatory cells; Mouse