Tanshinone IIA pretreatment attenuates hepatic ischemia-reperfusion.
Tanshinone IIA (Tan IIA), an active component derived from Salvia miltiorrhiza root, has been used to treat various ischemic cardiovascular and cerebrovascular diseases. However, its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. Here, we addressed this issue by using a 90-minute partial liver ischemia model. Mice were administered Tan IIA intragastrically for 3 days before ischemia and were assessed for liver damage 6-h after reperfusion. Tan IIA pretreatment significantly inhibited serum aminotransferases and proinflammatory cytokine levels along with reduced inflammatory infiltration and liver damage. Mechanistic studies revealed that Tan IIA suppressed TLR4 expression in nonparenchymal cells (NPCs) and induced heme oxygenase-1 (HO-1) production in both parenchymal and NPCs. Moreover, the phosphorylation of AKT and ERK1/2 in the liver was enhanced, while the phosphorylation of JNK, p38 and p65 was suppressed. These results suggest Tan IIA can suppress TLR4 signaling which then enhances HO-1 expression along with reduced proinflammatory cytokine expressions in the liver, and Tan IIA could be a useful candidate drug in clinic for prevention and treatment of hepatic I/R injury.
Department of General Surgery, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Yan-yan
YY
Qi
Liang
L
Xiao
Lu-ding
LD
Zhang
Shao-hua
SH
Song
Yi
Y
Mei
Teng
T
Chen
Jian-ming
JM
Tang
Fang
F
Liu
Guo-shan
GS
Ding
Yong-zhao
YZ
Shi
Quan-xing
QX
Wang
D045784:Abietanes / Q000627:therapeutic use*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000188:drug therapy*
D045784:Abietanes; D017931:DNA Primers; C021751:tanshinone