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

Feng Zhang, Jin Ling Shu, Ying Li, Yu Jing Wu, Xian Zheng Zhang, Le Han, Xiao Yu Tang, Chen Wang, Qingtong Wang, Jing Yu Chen, Yan Chang, Hua Xun Wu, Ling Ling Zhang, Wei Wei

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Paeoniflorin-6'-O-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, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ 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.

Original languageEnglish (US)
Article number933
JournalFrontiers in Pharmacology
Volume8
Issue numberDEC
DOIs
StatePublished - Dec 22 2017
Externally publishedYes

Keywords

  • BAFF
  • CP-25
  • Etanercept
  • Rituximab
  • Signaling pathway
  • TNF-alpha

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Zhang, F., Shu, J. L., Li, Y., Wu, Y. J., Zhang, X. Z., Han, L., Tang, X. Y., Wang, C., Wang, Q., Chen, J. Y., Chang, Y., Wu, H. X., Zhang, L. L., & Wei, W. (2017). 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. Frontiers in Pharmacology, 8(DEC), [933]. https://doi.org/10.3389/fphar.2017.00933