TY - JOUR T1 - Indigo fruits ingredient, aucubin protects against LPS-induced cardiac dysfunction in mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.119.259069 SP - jpet.119.259069 AU - Ming Xia Duan AU - Yuan Yuan AU - Chen Liu AU - Zhulan Cai AU - Qingwen Xie AU - Tongtong Hu AU - Qizhu Tang AU - Qing Qing Wu Y1 - 2019/01/01 UR - http://jpet.aspetjournals.org/content/early/2019/08/29/jpet.119.259069.abstract N2 - Inflammation, oxidative stress and apoptosis have been implicated in the pathogenesis of lipopolysaccharide (LPS)-induced cardiac dysfunction. Aucubin (AUB) has been found to possess anti-inflammatory and anti-apoptotic properties, but its effect on LPS-induced cardiac dysfunction is not clear. The present study investigated the effect of AUB on LPS-induced cardiac injury and the underlying molecular mechanism. Male C57BL/6 mice were received LPS injection (one 6 mg/kg injection of LPS) to induce cardiac dysfunction without or with AUB pretreatment (20 mg/kg or 80 mg/kg body weight per day) for 7 days. We found that AUB ameliorated cardiac dysfunction, inflammation, oxidative stress and apoptosis induced by LPS stimulation. AUB also decreased inflammatory cytokines expression, reduced oxidative stress and cell apoptosis induced by LPS stimulation in neonatal rat cardiomyocytes. Mechanically, we found that AUB inhibited thioredoxin interaction protein (TXNIP), NLRP3/ASC/caspase1 inflammasome formation in response to LPS stimulation in cardiomyocytes. Moreover, overexpression of NLRP3 in cardiomyocytes attenuated the protective effects of AUB. Interesting, NLRP3-deficiency exhibited ameliorated cardiac function and reduced inflammation response and oxidative stress after LPS insult in mice, while AUB could not further protect against LPS induced cardiac dysfunction in NLRP3-deficiency mice. In summary, AUB exerts a protective effect against LPS-induced cardiac dysfunction in an NLRP3 inflammasome-dependent manner. Hence, AUB might be a promising agent for the treatment of LPS-induced cardiac dysfunction.SIGNIFICANCE STATEMENT Aucubin exerts a protective effect against LPS-induced cardiac dysfunction by regulating NLRP3 inflammasome. ER -