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Hydroxysafflor yellow A attenuates ischemia/reperfusion-induced liver injury by
suppressing macrophage activation
#MMPMID24966974
Jiang S
; Shi Z
; Li C
; Ma C
; Bai X
; Wang C
Int J Clin Exp Pathol
2014[]; 7
(5
): 2595-608
PMID24966974
show ga
Hydroxysafflor yellow A (HSYA), a major constituent in the hydrophilic fraction
of the safflower plant, can retard the progress of hepatic fibrosis. However, the
anti-inflammatory properties and the underlying mechanisms of HSYA on I/R-induced
acute liver injury are unknown. Inhibiting macrophage activation is a potential
strategy to treat liver ischemia/reperfusion (I/R) injury. In this study, we
investigated the therapeutic effect of HSYA on liver I/R injury and the direct
effect of HSYA on macrophage activation following inflammatory conditions. The
therapeutic effects of HSYA on I/R injury were tested in vivo using a mouse model
of segmental (70%) hepatic ischemia. The mechanisms of HSYA were examined in
vitro by evaluating migration and the cytokine expression profile of the
macrophage cell line RAW264.7 exposed to acute hypoxia and reoxygenation (H/R).
Results showed that mice pretreated with HSYA had reduced serum transaminase
levels, attenuated inflammation and necrosis, reduced expression of inflammatory
cytokines, and less macrophage recruitment following segmental hepatic ischemia.
In vitro HSYA pretreated RAW264.7 macrophages displayed reduced migratory
response and produced less inflammatory cytokines. In addition, HSYA pretreatment
down-regulated the expression of matrix matalloproteinase-9 and reactive oxygen
species, and inhibited NF-?B activation and P38 phosphorylation in RAW264.7
cells. Thus, these data suggest that HSYA can reduce I/R-induced acute liver
injury by directly attenuating macrophage activation under inflammatory
conditions.