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

   
@article{APS9981,
	author = {Jin-ling Shu and Xian-zheng Zhang and Le Han and Feng Zhang and Yu-jing Wu and Xiao-yu Tang and Chen Wang and Yu Tai and Qing-tong Wang and Jing-yu Chen and Yan Chang and Hua-xun Wu and Ling-ling Zhang and Wei Wei},
	title = {Paeoniflorin-6′-O-benzene sulfonate alleviates collageninduced arthritis in mice by downregulating BAFF-TRAF2- NF-κB signaling: comparison with biological agents},
	journal = {Acta Pharmacologica Sinica},
	volume = {40},
	number = {6},
	year = {2019},
	keywords = {},
	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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/9981}
}