ReferenceID 6149

Rocaglamide Prolonged Allograft Survival by Inhibiting Differentiation of Th1/Th17 Cells in Cardiac Transplantation

Oxid Med Cell Longev

Background: Aglaia (Meliaceae) species are used for treating autoimmune disorders and allergic diseases in Asian countries. Rocaglamide, an extract obtained from Aglaia species, exhibits suppressive effect by regulating

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Reference Id
6149
Evidence Id
22739
Core Evidence Id
22739
Source Reference Id
5559
Herb2 Reference Id
HBREF006356
Subject Paper Key
HBIN042379_35087613
Pubmed Id
35087613
Doi
10.1155/2022/2048095
Paper Title
Rocaglamide Prolonged Allograft Survival by Inhibiting Differentiation of Th1/Th17 Cells in Cardiac Transplantation
Paper Abstract
Background: Aglaia (Meliaceae) species are used for treating autoimmune disorders and allergic diseases in Asian countries. Rocaglamide, an extract obtained from Aglaia species, exhibits suppressive effect by regulating the T cell subset balance and cytokine network in cancer. However, whether it can be used in organ transplantation is unknown. In this study, we investigated the antirejection effect and mechanism of action of rocaglamide in a mouse cardiac allograft model. Methods: Survival studies were performed by administering mice with phosphate-buffered saline (PBS) ( n = 6) and rocaglamide ( n = 8). Heart grafts were monitored until they stopped beating. After grafting, the mice were sacrificed on day 7 for histological, mixed lymphocyte reaction (MLR), enzyme-linked immunosorbent assay (ELISA), and flow cytometric analyses. Results: Rocaglamide administration significantly prolonged the median survival of the grafts from 7 to 25 days compared with PBS treatment ( P < 0.001). On posttransplantation day 7, the rocaglamide-treated group showed a significant decrease in the percentage of Th1 cells (7.9 ± 0.9% vs. 1.58 ± 0.5%, P < 0.001) in the lymph nodes and spleen (8.0 ± 2.5% vs. 2.4 ± 1.3%, P < 0.05). Rocaglamide treatment also significantly inhibited the production of Th17 cells (6.4 ± 1.0% vs. 1.8 ± 0.4%, P < 0.01) in the lymph nodes and spleen (5.9 ± 0.3% vs. 2.9 ± 0.8%, P < 0.01). Furthermore, the prolonged survival of the grafts was associated with a significant decrease in IFN- γ and IL-17 levels. Our results also showed that NF-AT activation was inhibited by rocaglamide, which also induced p38 and Jun N-terminal kinase (JNK) phosphorylation in Jurkat T cells. Furthermore, by using inhibitors that suppressed p38 and JNK phosphorylation, rocaglamide-mediated reduction in NF-AT protein levels was prevented. Conclusion: We identified a new immunoregulatory property of rocaglamide, wherein it was found to regulate oxidative stress response and reduce inflammatory cell infiltration and organ injury, which have been associated with the inhibition of NF-AT activation in T cells.
Journal
Oxid Med Cell Longev
Publish Year
2022
Experiment Subject
mouse; jurkat t cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Cancer; Autoimmune Disorders; Organ Injury; Allergic Diseases
Paper Title Cn
Paper Title En
Rocaglamide Prolonged Allograft Survival by Inhibiting Differentiation of Th1/Th17 Cells in Cardiac Transplantation
Bilingual Status
semi_complete