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 language | English (US) |
|---|---|
| Journal | Acta Pharmacologica Sinica |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling
T2 - comparison with biological agents
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
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - B cell
KW - BAFF
KW - collagen-induced arthritis
KW - etanercept
KW - paeoniflorin-6′-O-benzene sulfonate (CP-25)
KW - rituximab
KW - TRAF2
UR - http://www.scopus.com/inward/record.url?scp=85056694192&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056694192&partnerID=8YFLogxK
U2 - 10.1038/s41401-018-0169-5
DO - 10.1038/s41401-018-0169-5
M3 - Article
C2 - 30446734
AN - SCOPUS:85056694192
JO - Acta Pharmacologica Sinica
JF - Acta Pharmacologica Sinica
SN - 1671-4083
ER -