Berberine combined with cyclosporine A alleviates acute graft-versus-host disease in murine models
Autor: | Dingming Wan, Meng Wang, Hua-yan Zhao, Jing-lan Zhang, Zhongxing Jiang |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Berberine medicine.medical_treatment Immunology Anti-Inflammatory Agents Graft vs Host Disease Spleen Inflammation Hematopoietic stem cell transplantation Pharmacology medicine.disease_cause Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Immunology and Allergy Medicine Bone Marrow Transplantation Mice Inbred BALB C business.industry NF-kappa B Total body irradiation Mice Inbred C57BL Disease Models Animal Oxidative Stress surgical procedures operative 030104 developmental biology medicine.anatomical_structure Apoptosis Lymphocyte Transfusion 030220 oncology & carcinogenesis Acute Disease Cyclosporine Drug Therapy Combination Female Bone marrow medicine.symptom business Immunosuppressive Agents Oxidative stress Signal Transduction |
Zdroj: | International Immunopharmacology. 81:106205 |
ISSN: | 1567-5769 |
DOI: | 10.1016/j.intimp.2020.106205 |
Popis: | Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and the levels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell counts but had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD. |
Databáze: | OpenAIRE |
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