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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Pharmacol
2017 ; 8
(ä): 299
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Anhuienoside C Ameliorates Collagen-Induced Arthritis through Inhibition of MAPK
and NF-?B Signaling Pathways
#MMPMID28603496
Liu Q
; Xiao XH
; Hu LB
; Jie HY
; Wang Y
; Ye WC
; Li MM
; Liu Z
Front Pharmacol
2017[]; 8
(ä): 299
PMID28603496
show ga
Anemone flaccida Fr. Schmidt (Ranunculaceae) (Di Wu in Chinese) is used to treat
punch injuries and rheumatoid arthritis (RA). Our previous report has shown that
crude triterpenoid saponins from Anemone flaccida exhibited anti-arthritic
effects on type II collagen-induced arthritis in rats. Furthermore, anhuienoside
C (AC), a saponin compound isolated from A. flaccida, was observed to suppress
the nitric oxide production in lipopolysaccharide (LPS)-treated macrophage RAW
264.7 cells. In this study, we examined the effects of AC on the prevention and
treatment of collagen-induced arthritis in a mouse model and evaluated the
potential mechanisms involved. We observed that oral administration of AC
significantly suppressed the paw swelling and arthritic score, decreased the body
weight loss, and decreased the spleen index. Improvement in the disease severity
was accompanied by the reduction of cluster of differentiation 68 (CD68)-positive
cells in the ankle joint and inhibition of the pro-inflammatory cytokine tumor
necrosis factor alpha (TNF-?) in the synovium of the joint. Mechanistic studies
indicated that AC exerted its anti-inflammatory activity by inhibiting the mRNA
expression levels of inducible nitric oxide synthase, cyclooxygenase-2, TNF-?,
interleukin (IL)-1?, and IL-6 and by suppressing the production of inflammatory
cytokines such as TNF-?, IL-1?, and IL-6 in LPS-treated RAW 264.7 cells. AC also
blocked the LPS-induced activation of the extracellular signal-regulated kinase,
c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase pathways.
Additionally, the LPS-induced activation of nuclear factor kappa-B (NF-?B) was
significantly suppressed by AC treatment, as indicated by down-regulation of TLR4
and inhibition of the nuclear translocation of NF-?B p65 and by activation and
degradation of the inhibitor of kappa B. These findings indicated that AC has a
great potential to be developed as a therapeutic agent for human RA.