Verbascoside (VB) is a phenylethanoid glycoside extracted from the herbaceous plant Verbascum sinuatum and plays a neuroprotective role in Alzheimer’s disease (AD). The goal of this study was to explore the neuroprotective mechanism of VB. Based on the proteomics analysis, immunohistochemistry, immunofluorescence, Western blot, and ELISA were utilized to explore the neuroprotective mechanism of VB in context of neuroinflammation in APP/PS1 mice, LPS-induced BV2 cells, and/or Aβ1-42-stimulated N2a cells. Proteomic analysis demonstrated that the neuroprotection of VB correlated closely to its anti-inflammatory effect. VB significantly blocked microglia and astrocyte against activation in brains of APP/PS1 mice, suppressed the generation of IL-1β as well as IL-6, and boosted that of IL-4, IL-10 and TGF-β in vivo, which were analogous to results acquired in vitro. Furthermore, VB effectively restrained the phosphorylation of IKKα+β, IκBα, and NF-κB-p65 in APP/PS1 mice; LPS-induced BV2 cells, and Aβ1-42-stimulated N2a cells and lowered the tendency of NF-κB-p65 translocation towards nucleus in vitro. These results demonstrate that the neuroprotective effect of VB correlates to the modulation of neuroinflammation via NF-κB-p65 pathway, making VB as a hopeful candidate drug for the prevention and treatment of AD.
Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0–622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.
Owing to chronic radiotherapy and chemotherapy, cancer patients may suffer from immunosuppression, hematopoietic inhibition, and myelosuppression. 1 In this study, we first evaluated the effect of ZhenQi FuZheng formula (ZQFZ) on hematopoiesis in cells of mice with immunosuppression and hematopoietic dysfunction. The stability of the six effective constituents of ZQFZ according to the Chinese Pharmacopoeia (Version 2015) was first analyzed by high-performance liquid chromatography (HPLC) (Figure S1). Hematopoietic stem cells (HSCs) have been reported to maintain the hematopoietic function via the dynamic balance between their proliferation, the differentiation of red blood cells, and the formation of blood cells; thus, the agents that protect and/or improve the self-renewal of HSCs may be potential candidates for developing antimyelosuppression drugs. 1 ZQFZ strongly increased the proliferation of K562 cells (human myelogenous leukemia) and CHRF cells (human megakaryoblastic leukemia) (Figure 1A) without influencing their apoptosis (Figure 1C and D), motivated erythrocyte transformation (Figure 1B), and regulated the expressions of proteins, including P-RSK1-p90, c-Myc, and ETS transcription factor ELK1, which are associated with erythroid differentiation in the hematopoietic system (Figure 1E and F). In immunosuppressed mice established using cyclophosphamide (CTX) (75 mg/kg) injection, ZQFZ influenced the levels of immune function-related factors, including interleukins (ILs) and other serum cytokines (Table S1), relieved kidney damage (Figure 2A), and enhanced the activities of natural killer cells (Figure 2B), thereby demonstrating the immunoregulatory function of ZQFZ. The strong regulation of ILs, such as IL-2, inspired This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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