Description: |
Asarinin, a mammalian lignan precursor, has immunosuppression activity and can inhibit acute rejection in vitro. Asarinin may have a role on TLR4 pathway and produce prolongation of allograft heart survival. Asarinin induces dopamine biosynthesis via activation of the PKA-CREB-TH system and protects against 6-OHDA-induced cytotoxicity by inhibiting the sustained activation of the ERK-p38MAPK-JNK1/2-caspase-3 system in PC12 cells. |
Targets: |
TLR | CXCR | IL Receptor | PKA | cAMP | ERK | JNK | p38MAPK | Bcl-2/Bax | Caspase |
In vitro: |
Zhonghua xin xue Guan Bing za zhi,2003,31(6):444-447. | Experimental study of the effects of Asarinin on immunosuppression activity in vitro.[Reference: WebLink] | To test the extract of Asarum heterotropides called Asarinin in the immunosuppression activity in vitro and compared with cyclosporine A(CsA). METHODS AND RESULTS: Cardiomyocytes of adult wistar rats and spleen cells of adult SD rats were separated. 0.1 ml of the cardiomyocytes(2×10~(6)/ml) as stimulate cells and 0.1 ml of spleen cells(1×10~(7)/ml) as response cells were cultured in 96 culture plates. The model of rejection reaction in vitro was set up. Then the 0.1 ml serum including Asarinin was given to culture plates, the inhibition rate of lymphocyte transformation was investigated with MTT after 108 hours and IL-2、INF-#gamma#、IL-4 were detected with ELISA. Asarinin inhibited the lymphocyte transformation (inhibition rate 60.37%) in vitro. Compared with positive control group, it significantly decreased IL-2(69.11±17.47 pg/ml vs 160.44±19.79 pg/ ml, P<0.01)、INF-#gamma#(183.11± 95.24 pg/ml vs 521.89± 133.18 pg/ml, P<0.01) and increased IL-4(53.14±11.80 pg/ml vs 14.44± 4.21 pg/ml, P<0.01)in culture plates. |
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In vivo: |
Transplant Proc. 2015 Mar;47(2):545-8. | The effect of Asarinin on Toll-like pathway in rats after cardiac allograft implantation.[Pubmed: 25769604] | The objective of this study was to study the mechanism of the anti-rejection effect of Asarinin in rats that underwent cardiac allograft implantation.
METHODS AND RESULTS:
Hearts from Wistar rats were transplanted into the abdominal cavity of Sprague Dawley rats (SD rats) 64 SD rats received either cyclosporin A (CsA), Asarinin, or demi-dose of cyclosporine A and Asarinin through oral administration. On the seventh day post-transplantation, the expression of Toll-like receptor 4 (TLR4), chemokine (C-X-C motif) receptor 3 (CXCR3) in myocardium, and the level of interleukin (IL)-12 in the peripheral blood were analyzed 7 days after transplantation.
The survival time in 3 groups (CsA group, Asarinin group, and semi-dose CsA group) prolonged (P < .01), the microscope myocardial histopathology in 3 groups (CsA group, Asarinin group and semi-dose CsA group) relieved, the expression of TLR4 and CXCR3 in 3 groups was significantly decreased (P < .01) when compared with the control group. The level of IL-12 decreased remarkably (P < .05) in the 3 groups when compared with the control group.
CONCLUSIONS:
The combined data suggested that Asarinin decreased peripheral blood concentration of IL-12 and inhibited the expression of TLR4 and CXCR3, which means Asarinin may have a role on TLR4 pathway and produced prolongation of allograft heart survival. |
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