Total Flavonoids of Anchusa italica Retz. Inhibit Activation of Inflammasome through ROS/TXNIP/NLRP3 Pathway to Protect against Myocardial Ischemia-reperfusion Injury
YIN Su-yue, JIANG Yu, WANG Dan-shu, YAN Liu-yan, WANG Shou-bao*, DU Guan-hua*
Beijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Abstract:OBJECTIVE To investigate the role of activation of NLRP3 inflammasome and ROS/TXNIP/NLRP3 pathway in the effects of total flavonoids of Anchusa italica Retz. (TF) against myocardial ischemia-reperfusion injury (MIRI). METHODS The ligation of left coronary artery was used to mimic MIRI in mice. Thirty mice were randomly divided into I/R group, 30 mg·kg-1 TF treatment group (I/R+TF30) and 100 mg·kg-1 treatment group (I/R+TF100). At 24 h after reperfusion, cardiac function, myocardial infarct index and serum myocardial enzyme were measured. The activation of NLRP3 inflammasome, ROS level and TXNIP/NLRP3 interaction were observed. RESULTS TF treatment at the doses of 30 and 100 mg·kg-1 improved cardiac function, reduced myocardial infarct index, showing obvious myocardial protection. In addition, TF treatment reduced the levels of inflammatory cytokines IL-1 β, IL-6 and TNF-α, and decreased ROS content in myocardial tissue. The levels of TXNIP, NLRP3, cleaved caspase-1 and cleaved IL-1 β were significantly decreased in I/R+TF30 and I/R+TF100 groups, and the TXNIP/NLRP3 interaction was also inhibited as compared with I/R group. CONCLUSION TF treatment exertes potent protection against MIRI in mice, in which inhibition of activation of NLRP3 inflammasome via the ROS/TXNI/NLRP3 pathway played a pivotal role.
阴苏月, 姜瑜, 王丹姝, 燕柳艳, 王守宝, 杜冠华. 牛舌草总黄酮通过ROS/TXNIP/NLRP3抑制炎症小体活化抗心肌缺血再灌注损伤[J]. 中国药学杂志, 2021, 56(14): 1131-1137.
YIN Su-yue, JIANG Yu, WANG Dan-shu, YAN Liu-yan, WANG Shou-bao, DU Guan-hua. Total Flavonoids of Anchusa italica Retz. Inhibit Activation of Inflammasome through ROS/TXNIP/NLRP3 Pathway to Protect against Myocardial Ischemia-reperfusion Injury. Chinese Pharmaceutical Journal, 2021, 56(14): 1131-1137.
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