Naoxintong attenuates Ischaemia/reperfusion Injury through inhibiting NLRP3 inflammasome activation

• Published in: Journal of cellular and molecular medicine 2017-01, Vol.21 (1), p.4-12
• Main Authors: Wang, Yaqiong, Yan, Xiaoxiang, Mi, Shouling, Li, Zhang, Wang, Yuexiang, Zhu, Hong, Sun, Xiaolei, Zhao, Buchang, Zhao, Chao, Zou, Yunzeng, Hu, Kai, Ding, Xiaoqiang, Sun, Aijun, Ge, Junbo
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis Regulatory Proteins - metabolism; Caspase 1 - metabolism; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Inflammasomes - drug effects; Inflammasomes - metabolism; inflammation; Interleukin-1beta - blood; Interleukin-1beta - metabolism; ischaemia reperfusion injury; macrophage polarity; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Myocardial Reperfusion Injury - blood; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; naoxintong; Neutrophil Infiltration - drug effects; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Original; Reperfusion Injury - blood; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Signal Transduction - drug effects
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12915

Naoxintong (NXT) is a Chinese Materia Medica standardized product extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinensis, Astragali Radix. Naoxintong is clinically effective in treating ischaemia heart disease. Nucleotide‐binding oligomerization domain‐Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome has been critically involved in myocardial ischaemia/reperfusion (I/R) injury. Here, we have been suggested that NXT might attenuate myocardial I/R injury via suppression of NLRP3 inflammasome activation. Male C57BL6 mice were subjected to myocardial I/R injury via 45 min. coronary ligation and release for the indicated times. Naoxintong (0.7 g/kg/day) and PBS were orally administrated for 2 weeks before surgery. Cardiac function assessed by echocardiography was significantly improved in the NXT group compared to PBS group at day 2 after myocardial I/R. NLRP3 inflammasome activation is crucially involved in the initial inflammatory response after myocardial I/R injury, leading to cleaved caspase‐1, mature interleukin (IL)‐1β production, accompanying by macrophage and neutrophil infiltration. The cardioprotective effect of NXT was associated with a diminished NLRP3 inflammasome activation, decreased pro‐inflammatory macrophage (M1 macrophages) and neutrophil infiltration after myocardial I/R injury. In addition, serum levels of IL‐1β, indicators of NLRP3 inflammasome activation, were also significantly suppressed in the NXT treated group after I/R injury. Naoxintong exerts cardioprotive effects at least partly by suppression of NLRP3 inflammasome activation in this I/R injury model.