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Effects of Glycyrrhizic Acid in Licorice on Prolongation of Murine Cardiac Allograft Survival
Institution:1. Department of Cardiovascular Surgery, Teikyo University, Tokyo, Japan;2. Department of Medicine, Emory University, Atlanta, Georgia;3. Department of Surgery, Teikyo University, Tokyo, Japan;1. Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;2. Department of Anesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, Korea;1. Department of Plastic and Reconstructive Surgery, School of Medicine, Kangwon National University Hospital, Chuncheon, Korea;2. Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Korea;1. Department of Surgery, Japanese Red Cross Kumamoto Hospital, Kumamoto, Kumamoto, Japan;2. Department of Nephrology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Kumamoto, Japan;3. Department of General Internal Medicine, Japanese Red Cross Kumamoto Hospital, Kumamoto, Kumamoto, Japan;4. Department of Gastroenterology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Kumamoto, Japan;5. Department of Urology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Kumamoto, Japan;1. Department of Nephrology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia;2. Department of Nephrology, Selayang Hospital, Selangor, Malaysia;1. Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto-prefecture, Japan;2. Wakunaga Pharmaceutical Co, Ltd Molecular Diagnostics Division, 1624 Shimokotachi, Koda-cho, Akitakata, Hiroshima, Japan
Abstract:Recent evidence has pointed to the promising benefits of using specific immunosuppressive herbal compounds to prolong transplant allograft survival. In this study, we investigated the effects of glycyrrhizic acid (GA), a major component of licorice, in a model of murine heart transplantation. CBA (H2k) mice were transplanted with a fully-MHC mismatched C57BL/6 (H2b) heart allograft and subsequently received daily intraperitoneal administration of normal saline or 0.02, 0.2, or 2.0 mg/d of GA for 7 consecutive days. Untreated CBA recipients, with a median survival time (MST) of 7 days, and groups receiving 0.02mg/d (MST, 8 days) or 0.2mg/d (MST, 9 days) of GA acutely rejected C57BL/6 cardiac allografts. But mice treated with 2.0 mg/d of GA demonstrated significant prolongation of allografts (MST, 23 days). Histologic studies showed that cardiac allografts from GA-treated CBA recipients had preserved graft and vessel structure. Moreover, flow cytometric study showed that the percentage of CD4+CD25+Foxp3+ cell (regulatory T cell Treg]) populations were increased in GA-treated CBA recipients. In a mixed leukocyte culture, splenocytes from GA-treated mice demonstrated suppressed allo-proliferation, in which interleukin (IL)-2 and interferon gamma production were downregulated and IL-10 secretion was upregulated. In conclusion, GA may be a novel promising therapeutic agent to prolong cardiac allograft survival through direct anti-inflammatory effects and induction of Treg populations.
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