Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

• Published in: BMC complementary and alternative medicine Vol. 24; no. 1; pp. 186 - 12
• Main Authors: Xu, Wencheng, Chen, Shuhe, Wang, Xiaoqin, Min, Jinwen, Tanaka, Sachiko, Onda, Kenji, Sugiyama, Kentaro, Yamada, Haruki, Hirano, Toshihiko
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.05.2024; BioMed Central; BMC
• Subjects: Alopecia; Antibodies; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Baldness; Benzodioxoles; Benzylisoquinolines - pharmacology; Blood; CD25 antigen; CD4 antigen; CD8 antigen; Cells; Cepharanthine; Chronic illnesses; Corticosteroids; Cytokines; Cytoplasm; Daunorubicin; Drug Synergism; Efflux; Flow cytometry; Foxp3 protein; Glucocorticoid receptor; Glucocorticoid receptors; Glucocorticoids; Glycoproteins; Helper cells; Humans; Idiopathic thrombocytopenic purpura; Immune system; Immunoregulation; Interleukins; Leukemia; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Methylprednisolone; Methylprednisolone - pharmacology; Molecular modelling; Molting; P-Glycoprotein; Penicillin; peripheral blood mononuclear cell; Peripheral blood mononuclear cells; Pharmacodynamics; Pharmacology; Political aspects; Receptors; Receptors, Glucocorticoid - metabolism; Rhodamine; Software; T cells; Thrombocytopenia; Translocation; Tumor necrosis factor-α; γ-Interferon; Japan; United States > US; P-glycoprotein; Cepharanthine; Methylprednisolone; peripheral blood mononuclear cell; Glucocorticoid receptor
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-024-04489-z

Cepharanthin alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin . The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions. Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4 CD25 Foxp3 regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot. CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 μM of CEP significantly inhibited P-glycoprotein efflux function of CD4 cells, CD8 cells, and lymphocytes (P<0.05). 0.03~3 μM of CEP also inhibited the P-glycoprotein efflux function in MOLT-4/DNR cells in a concentration-dependent manner (P<0.001). However, 0.03~3 μM of CEP did not influence P-glycoprotein expression. 0.03~0.3 μM of CEP significantly increased the GC receptor distribution from the cytoplasm to the nucleus in a concentration-dependent manner in MOLT-4/DNR cells. The combination did not influence the frequency of CD4 , CD4 CD25 and CD4 CD25 Foxp3 T cells or the secretion of Th1/Th2/Th17 cytokines from PBMCs. In contrast, CEP alone at 1 μM decreased the percentage of CD4 T cell significantly (P<0.01). It also inhibited the secretion of IL-6, IL-10, IL-17, TNF-α, and IFN-γ. CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin alone or in combination with GC for the management of chronic ITP.