• Aplastic anemia
• Bone marrow
• Ginsenoside Rg1
• Hematopoietic stem cells
• MAPK signaling pathway
• Myelosuppression

• Chinese materia medica
• aplastic anemia
• mechanism
• traditional Chinese medicine
• treatment

• Humans
• Anemia, Aplastic/drug therapy
• Medicine, Chinese Traditional
• Immunosuppression Therapy
• Recurrence
• Immunosuppressive Agents/therapeutic use
• Immunosuppressive Agents/adverse effects

Bushen Jianpi Quyu Formula (BSJPQYF), an experienced formula, has been used to treat aplastic anemia (AA) more than three decades. To determinate the effect of BSJPQYF on AA, we constructed an immune-mediated AA mouse model. All mice were divided into four groups: control, model, low dose (0.85 g/mL), and high dose (1.7 g/mL BSJPQYF) group. They were administered with different concentrations of BSJPQYF or normal saline for 14 days. Besides, components of BSJPQYF were analyzed by electrospray ionization and mass spectrometry (ESI-MS). Subsequently, mouse peripheral blood and femurs were collected, and bone marrow mesenchymal stem cells (BMSCs) were isolated by fluorescence-activated cell sorting (FACS). Among them, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ) were measured by ELISA assay, PI3K, AKT, p-AKT, NF-κB, p-NF-κB, TNF-α, and cleaved caspase-3 proteins were detected by western blot. Compared with standard compounds, we identified three compounds of BSJPQYF, namely, icariin, kaempferol and tanshinone iia, as potentially effective compounds for the treatment of AA. Through an in vivo study, we found the administration of BSJPQYF in high dose for 14 days could significantly increase peripheral blood count and bone marrow (BM) cells, meanwhile decrease TNF-α, TGF-β, and IFN-γ levels. Besides, it could suppress the protein expression of PI3K and the phosphorylation of AKT and NF-κB to restrict the protein expression of TNF-α, eventually reduce the protein expression of cleaved caspase-3. This study demonstrated the therapeutic effects of BSJPQYF in AA, which could alleviate myelosuppression through inhibiting the expression of the PI3K/AKT/NF-κB signaling pathway.

To better understanding and differentiation of traditional Chinese medicine (TCM) syndromes in severe aplastic anemia (SAA) patients undergoing hematopoietic stem cell transplantation (Allo-HSCT) and their correlation with iron metabolism, cAMP/cGMP, 17-OH-CS and thyroxine.

Eighteen patients with SAA who underwent HSCT were enrolled. The syndrome was evaluated before conditioning and days after stem cell reinfusion (−10d, −1d, +7d, +30d, +60d, and +90d). The correlation of TCM syndrome (Yin, Yang, and stasis) to cyclic nucleotides, 17-OH-CS, thyroxine, and iron metabolism were analyzed and compared to data from normal subjects.

More “Yin deficiency” (n=11, 11/18) syndrome was observed before HSCT, and nearly 61% was complicated with “blood stasis”. After conditioning, the proportion of “kidney Yin and Yang deficiency” increased to 61.6%. Fourteen days after HSCT, the syndrome developed into “Spleen-Kidney Yang Deficiency,” and the stasis score decreased. On +90day, majority patients were diagnosed with “Kidney Yang Deficiency” (35.7%) or “Spleen-Kidney Yang Deficiency” (28.6%), and 88.9% were diagnosed without stasis. The correlation analysis showed that cGMP might represent “Deficient Yang” as well as low total triiodothyronine (T3) and free T3 (FT3). There was also a positive relation between labile plasma iron (LPI), hepcidin, soluble transferrin receptor (sTfR), and “Yin deficiency”, and the last two factors, along with marrow nitric oxide synthase were also positively related to “Stasis” syndrome.

During HSCT, the syndrome evolved from “kidney Yin and Yang deficiency” to “kidney Yang deficiency” or “spleen–kidney Yang deficiency”, and the “stasis” along with “Yin deficiency” syndromes were quickly relieved within 90 days. The changes of cyclic nucleotides, 17-OH-CS, thyroxine, and iron metabolism indexes can be applied for better differentiation of TCM syndrome.

• aplastic anemia
• hematopoietic stem cell transplantation
• iron metabolism
• syndrome evolution
• traditional Chinese medicine syndrome

To explore the clinical efficacy and mechanism of compound Shenlu granule (SLG) treatment in patients with aplastic anemia (AA).

A total of 89 AA patients were randomly divided into an SLG supportive group (group A, n = 44) and a control group (group B, n = 45) while continuing Western medical management. After 6 months, hemograms, traditional Chinese medicine (TCM) syndrome scores, and overall clinical efficacy rate were assessed. Serum metabolomics characteristics were observed using ultraperformance liquid chromatography-mass spectrometry after SLG intervention.

The levels of red blood cell (RBC), hemoglobin (Hb), and platelet (PLT) were increased in both groups after treatment for 6 months (P < 0.05), and in group A, the elevation of PLT became much more significant (P < 0.01). The TCM syndrome score was lower in group A than in group B after treatment (P < 0.05). Metabolomics data showed a significant difference in the patients using SLG after 6 months, and 14 biomarkers were identified.

SLG supportive treatment showed positive results in patients with AA, and metabolomics data indicated that SLG influenced aminoacyl-tRNA biosynthesis and glycerophospholipid metabolism to gradually return to normal.

• Jianpi Bushen therapy
• Traditional Chinese Medicine
• chronic kidney disease anemia
• meta-analysis
• randomized controlled trials (RCT)

• Chinese drugs
• aplastic anemia
• review
• traditional Chinese medicine treatment

Iron overload is commonly observed during the course of aplastic anemia (AA), which is believed to aggravate hematopoiesis, cause multiple organ dysfunction, lead to disease progression, and impair quality of life. Deferasirox (DFX) and deferoxamine (DFO) are among the most common iron chelation agents available in the clinical setting. The aim of this study was to investigate if the combination therapy with DFX and DFO is superior in hematopoietic recovery and iron chelation.

Briefly, we developed a composite mouse model with AA and iron overload that was consequently treated with DFX, DFO, or with a combination of both agents. The changes in peripheral hemogram, marrow apoptosis, and its related protein expressions were compared during the process of iron chelation, while the iron depositions in liver and bone marrow and its regulator were also detected.

The obtained results showed that compared to DFX, DFO has a better effect in protecting the bone marrow from apoptosis-induced failure. The combination of DFO and DFX accelerated the chelation of iron, while their efficiency on further hemogram improvement appeared limited.

To sum up, our data suggest that single treatment with DFO may be a better choice for improving the hematopoiesis during the gradual chelation treatment irrespective of the convenience of oral DFX, while the combination treatment should be considered for urgent reduction of the iron burden.

• animal model
• aplastic anemia
• deferasirox
• deferoxamine
• iron overload
• mouse

Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.

• animal model
• aplastic anemia
• iron overload
• mouse