Abstract
A previous study conducted by our group demonstrated that Radix Astragali compounded with Codonopsis pilosula and Plastrum testudinis was effective in treating pediatric β-thalassemia in a randomized, controlled clinical trial. However, the mechanism of action that underpins this treatment remains to be elucidated. Blood was collected from patients participating in this clinical trial and nucleated red blood cell-enriched mononuclear cells were isolated to facilitate the extraction of RNA and protein. RT-PCR was used to monitor the expression of globin genes and p38 MAPK, and total and phosphorylated p38 MAPK expression was assessed using Western blot analysis. Expression of α-, β-, and Aγ-globin mRNAs was not significantly affected following treatment with R. Astragali or the compounded formulation. However, Gγ-globin mRNA levels increased significantly in both treatment groups (when compared with pretreatment levels) following 12 weeks of treatment. Moreover, posttreatment Gγ-globin expression was significantly higher in both treatment groups compared with the control group. Although neither p38 MAPK mRNA nor protein levels were affected by the treatments, posttreatment phosphorylation of p38 MAPK was significantly increased in the R. Astragali and compounded formulation groups compared with the control group. These data suggest that the molecular mechanisms that underpin the efficacious use of R. Astragali (and its compounded formulation) in pediatric β-thalassemia treatment facilitate the induction of Gγ-globin expression following activation of p38 MAPK.
Highlights
Hemoglobin (Hb) disorders, β-thalassemia, are the most common single gene disorders caused by mutations in the β-globin locus
Clinical management of β-thalassemia patients includes lifelong blood transfusions and chelation therapy to remove excess transfused iron [1] and, in some cases, bone marrow transplantation [2, 3]. β-Thalassemia syndromes are classified according to severity based on steady-state Hb and transfusion dependency. β-Thalassemia major and β-thalassemia intermedia are both caused by the inheritance of two β-globin gene mutations [4]
Astragali (AMW), 11 patients were treated with the compounded formulation (AMW + Codonopsis pilosula granule [CPG] + Plastrum testudinis granule [PTG]), and 11 patients were treated with a placebo
Summary
Hemoglobin (Hb) disorders, β-thalassemia, are the most common single gene disorders caused by mutations in the β-globin locus. Resultant disorders cause abnormal or reduced adult hemoglobin (HbA) production and excess, unmatched α-chains in developing erythroblasts. Clinical symptoms include bone marrow expansion, splenomegaly, and a severe anemia that requires regular blood transfusions. Clinical management of β-thalassemia patients includes lifelong blood transfusions and chelation therapy to remove excess transfused iron [1] and, in some cases, bone marrow transplantation [2, 3]. An increase in HbF levels can functionally compensate for the shortfall in HbA synthesis in β-thalassemia patients and synthesized γ-chains can neutralize excess unbalanced αchains to reduce erythrocyte damage and ameliorate anemia
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