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Plant‐derived alkaloid sinomenine potentiates glucocorticoid pharmacodynamics in mitogen‐activated human peripheral blood mononuclear cells by regulating the translocation of glucocorticoid receptor
Author(s) -
Xu Wencheng,
Wang Xiaoqin,
Tu Yuanchao,
Masaki Hiroshi,
Tanaka Sachiko,
Onda Kenji,
Sugiyama Kentaro,
Yamada Haruki,
Hirano Toshihiko
Publication year - 2019
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6215
Subject(s) - sinomenine , methylprednisolone , pharmacology , glucocorticoid receptor , peripheral blood mononuclear cell , glucocorticoid , jurkat cells , pharmacodynamics , chemistry , medicine , endocrinology , immunology , in vitro , pharmacokinetics , biochemistry , t cell , immune system
Sinomenine has been used as an antirheumatic drug in China. Glucocorticoid combined with sinomenine could be an alternative therapeutic approach. In this study, we evaluated the sinomenine potential effect on glucocorticoid pharmacodynamics in vitro using a human peripheral blood mononuclear cell (PBMC) culture system. We also disclosed the possible action mechanism of sinomenine with a focus on P‐glycoprotein function and glucocorticoid receptor (GR) translocation into nucleus. The median (range) of methylprednisolone IC 50 values against the PBMC proliferation was 3.18 (0.45–6.81) ng/mL, whereas the median (range) IC 50 values of methylprednisolone combined with 0.03, 0.3, 3, and 30 μM sinomenine were 1.85 (0.05–5.15), 0.83 (0.10–3.90), 0.56(0.09–1.62), and 0.59(0.05–1.30) ng/mL, respectively. Sinomenine significantly decreased the IC 50 values of methylprednisolone and enhanced the immunosuppressive effect of methylprednisolone ( p < 0.05). Sinomenine alone regulated the GR translocation in both Jurkat T cells and normal human PBMCs, and the combination of sinomenine and methylprednisolone showed stronger GR‐modulatory activity than methylprednisolone alone. Thus, the additive effect of sinomenine to promote the methylprednisolone immunosuppressive efficacy was suggested to be related to nuclear GR‐translocation. However, sinomenine did not significantly inhibit the P‐glycoprotein function in the activated PBMCs, suggesting that sinomenine's additive effect seemed to be unrelated with the P‐glycoprotein inhibition.