CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells Through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

Overview

Journal Front Pharmacol

Date 2018 Jan 10

PMID 29311935

Citations 9

Authors

Feng Zhang

Jin-Ling Shu

Ying Li

Yu-Jing Wu

Xian-Zheng Zhang

Le Han

Xiao-Yu Tang

Chen Wang

Qing-Tong Wang

Jing-Yu Chen

Yan Chang

Hua-Xun Wu

Ling-Ling Zhang

Wei Wei

Affiliations

Soon will be listed here.

Abstract

Paeoniflorin-6'--benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 B cells, CD19CD20 B cells, CD19CD27 B cells and CD19CD20CD27 B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

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