Bushen Jianpi Quyu Formula Alleviates Myelosuppression of an Immune-Mediated Aplastic Anemia Mouse Model via Inhibiting Expression of the PI3K/AKT/NF-κB Signaling Pathway

Abstract

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.

Formononetin reverses immune-mediated TregTh17 immune imbalance in Immune-mediated bone marrow failure mice by regulating the PI3KAkt signaling pathway

“…RuiLan Gao et al found that ginsenosides improved iron overload-induced apoptosis in a mouse model of aplastic anemia (AA) by activating the PI3K/Akt/mTOR pathway [33] . Baodong Ye et al discovered that the Bushen Jianpi Quyu formula improved bone marrow suppression in an AA mouse model by inhibiting the PI3K/Akt/NF-κB signaling pathway [36] . In the present study, we also investigated the effect of FMN on PI3K/Akt pathway.…”

Formononetin reverses Treg/Th17 imbalance in immune-mediated bone marrow failure mice by regulating the PI3K/Akt signaling pathway

“…Modern pharmacological studies have reported that FMN possesses anti-inflammatory, antimicrobial, antioxidant, anticancer and immunomodulatory properties [ 21 ]. It has been confirmed that Huangqi could regulate the balance of Treg/Th17 cells in inflammatory diseases, such as asthma and colitis [ 22 – 24 ]. FMN could modulate the differentiation of Th17 cells and facilitate the development of Treg cells in mice with estrogen deficiency-induced osteoporosis and consequently alleviate bone loss [ 25 ].…”

Analysis of adverse drug reactions/events of cancer chemotherapy and the potential mechanism of Danggui Buxue decoction against bone marrow suppression induced by chemotherapy

“…This helped to further reveal the mechanism of DBD in preventing a certain injury disease caused by chemotherapy and provided theoretical support and a scientific foundation for in-depth clinical research and application ( Sun et al, 2023 ; Zhao et al, 2023 ). Systems biology is the technological theory on which network pharmacology is built, which can be used to do network topology analysis, develop the drug target disease network relationship, discover medications for disease treatment, searche the network database, forecast the drug treatment mechanism, and create a thorough network study of medication effects from various levels and viewpoints starting with a multi-target research method ( Hopkins AL., 2007 ; Li et al, 2022 ).…”