Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents

Jin ling Shu, Xian zheng Zhang, Le Han, Feng Zhang, Yu jing Wu, Xiao yu Tang, Chen Wang, Yu Tai, Qingtong Wang, Jing yu Chen, Yan Chang, Hua xun Wu, Ling ling Zhang, Wei Wei

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Paeoniflorin-6′-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days. In CIA mice, we found that T cells and B cells exhibited abnormal proliferation; the percentages of CD19+ total B cells, CD19+CD27+-activated B cells, CD19+BAFFR+ and CD19+TACI+ cells were significantly increased in PBMCs and spleen lymphocytes. CP-25 suppressed the indicators of arthritis, alleviated histopathology, accompanied by reduced BAFF and BAFF receptors expressions, inhibited serum immunoglobulin levels, decreased the B-cell subsets percentages, and prevented the expressions of key molecules in NF-κB signaling. Furthermore, we showed that treatment with CP-25 reduced CD19+TRAF2+ cell expressions stimulated by BAFF and decreased TRAF2 overexpression in HEK293 cells in vitro. Thus, CP-25 restored the abnormal T cells proliferation and B-cell percentages to the normal levels, and normalized the elevated levels of IgA, IgG2a and key proteins in NF-κB signaling. In comparison, rituximab and etanercept displayed stronger anti-inflammatory activities than CP-25; they suppressed the elevated inflammatory indexes to below the normal levels in CIA mice. In summary, our results provide evidence that CP-25 alleviates CIA and regulates the functions of B cells through BAFF-TRAF2-NF-κB signaling. CP-25 would be a soft immunomodulatory drug with anti-inflammatory effect.

Original languageEnglish (US)
JournalActa Pharmacologica Sinica
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

TNF Receptor-Associated Factor 2
Experimental Arthritis
Biological Factors
B-Lymphocytes
Down-Regulation
B-Cell Activation Factor Receptor
Anti-Inflammatory Agents
B-Cell Activating Factor
B-Lymphocyte Subsets
T-Lymphocytes
HEK293 Cells
Therapeutic Uses
Solubility
Immunoglobulin A
Biological Availability
Arthritis
Immunoglobulins
Esters
Spleen
Cell Proliferation

Keywords

  • B cell
  • BAFF
  • collagen-induced arthritis
  • etanercept
  • paeoniflorin-6′-O-benzene sulfonate (CP-25)
  • rituximab
  • TRAF2

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling : comparison with biological agents. / Shu, Jin ling; Zhang, Xian zheng; Han, Le; Zhang, Feng; Wu, Yu jing; Tang, Xiao yu; Wang, Chen; Tai, Yu; Wang, Qingtong; Chen, Jing yu; Chang, Yan; Wu, Hua xun; Zhang, Ling ling; Wei, Wei.

In: Acta Pharmacologica Sinica, 01.01.2018.

Research output: Contribution to journalArticle

Shu, Jin ling ; Zhang, Xian zheng ; Han, Le ; Zhang, Feng ; Wu, Yu jing ; Tang, Xiao yu ; Wang, Chen ; Tai, Yu ; Wang, Qingtong ; Chen, Jing yu ; Chang, Yan ; Wu, Hua xun ; Zhang, Ling ling ; Wei, Wei. / Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling : comparison with biological agents. In: Acta Pharmacologica Sinica. 2018.
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abstract = "Paeoniflorin-6′-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days. In CIA mice, we found that T cells and B cells exhibited abnormal proliferation; the percentages of CD19+ total B cells, CD19+CD27+-activated B cells, CD19+BAFFR+ and CD19+TACI+ cells were significantly increased in PBMCs and spleen lymphocytes. CP-25 suppressed the indicators of arthritis, alleviated histopathology, accompanied by reduced BAFF and BAFF receptors expressions, inhibited serum immunoglobulin levels, decreased the B-cell subsets percentages, and prevented the expressions of key molecules in NF-κB signaling. Furthermore, we showed that treatment with CP-25 reduced CD19+TRAF2+ cell expressions stimulated by BAFF and decreased TRAF2 overexpression in HEK293 cells in vitro. Thus, CP-25 restored the abnormal T cells proliferation and B-cell percentages to the normal levels, and normalized the elevated levels of IgA, IgG2a and key proteins in NF-κB signaling. In comparison, rituximab and etanercept displayed stronger anti-inflammatory activities than CP-25; they suppressed the elevated inflammatory indexes to below the normal levels in CIA mice. In summary, our results provide evidence that CP-25 alleviates CIA and regulates the functions of B cells through BAFF-TRAF2-NF-κB signaling. CP-25 would be a soft immunomodulatory drug with anti-inflammatory effect.",
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AU - Shu, Jin ling

AU - Zhang, Xian zheng

AU - Han, Le

AU - Zhang, Feng

AU - Wu, Yu jing

AU - Tang, Xiao yu

AU - Wang, Chen

AU - Tai, Yu

AU - Wang, Qingtong

AU - Chen, Jing yu

AU - Chang, Yan

AU - Wu, Hua xun

AU - Zhang, Ling ling

AU - Wei, Wei

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