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Published on: January 2, 2017
C. sinensis ablates allograft vasculopathy when used as an adjuvant therapy with cyclosporin A
J L Jordan1, G M Hirsch, T D G Lee
1Department of Pathology, Dalhousie University, 5850 College Street, Halifax NS B3H 1X5, Canada.
Insights
Traditional Chinese Medicine Cordyceps sinensis shows promise in reducing cardiac transplant rejection. This study found C. sinensis extract can decrease acute rejection and CD8+ T cell activity, offering potential for long-term graft survival.
Area of Science:
- Immunology
- Pharmacology
- Transplantation Medicine
Background:
- Current immunosuppressants like calcineurin inhibitors cause significant pathologies.
- There is a need for novel therapeutics to address long-term cardiac graft failure.
- Traditional Chinese Medicines (TCM) are being explored as sources for new treatments.
Purpose of the Study:
- To evaluate Cordyceps sinensis (C. sinensis) for reducing acute and chronic cardiac transplant rejection.
- To determine if oral C. sinensis extract can reduce acute rejection in a rat heart transplant model.
- To assess the in vitro effect of C. sinensis extract on CD8+ T cell activity and its ability to ablate allograft vasculopathy.
Main Methods:
- A rat heterotopic heart transplant model was used to assess acute rejection.
- In vitro mixed lymphocyte reactions were employed to measure CD8+ T cell activity.
- A mouse abdominal aortic transplant model was utilized to evaluate allograft vasculopathy.
Main Results:
- Oral C. sinensis extract reduced acute rejection when combined with sub-therapeutic Cyclosporine.
- The extract significantly decreased CD8+ T cell activity in vitro.
- Combined with therapeutic Cyclosporine, C. sinensis oral delivery ablated allograft vasculopathy.
Conclusions:
- Cordyceps sinensis demonstrates potential as an adjuvant therapy in cardiac transplantation.
- C. sinensis may offer a novel approach to mitigate both acute and chronic transplant rejection.
- Further research into C. sinensis could lead to improved long-term outcomes for cardiac transplant recipients.
Abstract:
Immunosuppressive treatments are available to suppress acute cardiac rejection; however, no viable treatment exists for long-term cardiac graft failure. Moreover, extended use of calcineurin inhibitor immunosuppressants, the mainstay of the current therapeutic for cardiac transplantation, leads to significant associated pathologies such as nephrotoxicity and increased risk of cardiac disease. For the last ten years alternatives to calcineurin inhibitors, or adjuvant therapies designed to complement their activities, have been explored. In tandem with this development, there has been considerable interest in Traditional Chinese Medicines (TCM) as sources for novel therapeutics. Our study examines the ability of the TCM Cordyceps sinensis to reduce acute and chronic rejection associated with cardiac transplantation. The objectives of this study were to first determine if oral delivery of the extract could reduce acute rejection in a rat heterotopic heart model of transplantation. The second objective was to determine, in vitro, if a sterile, aqueous extract of C. sinensis could decrease CD8+ T cell activity. The third objective was to determine if oral delivery of the extract could ablate allograft vasculopathy in a mouse abdominal aortic transplant model. We found that oral delivery of the extract demonstrated a reduction in acute rejection when used in conjunction with a sub-therapeutic dose of Cyclosporine. Further, we found, using a mixed lymphocyte reaction, that the extract was able to significantly reduce CD8+ T cell activity. Finally, we demonstrate that oral delivery of the extract, used with a therapeutic dose of Cyclosporine to suppress acute rejection, ablates allograft vasculopathy.
