PT  - JOURNAL ARTICLE
AU  - MingXia Duan
AU  - Yuan Yuan
AU  - Chen Liu
AU  - Zhulan Cai
AU  - Qingwen Xie
AU  - Tongtong Hu
AU  - Qizhu Tang
AU  - QingQing Wu
TI  - Indigo Fruits Ingredient, Aucubin, Protects against LPS-Induced Cardiac Dysfunction in Mice
AID  - 10.1124/jpet.119.259069
DP  - 2019 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 348--359
VI  - 371
IP  - 2
4099  - http://jpet.aspetjournals.org/content/371/2/348.short
4100  - http://jpet.aspetjournals.org/content/371/2/348.full
SO  - J Pharmacol Exp Ther2019 Nov 01; 371
AB  - Aucubin (AUB), which is extracted from Eucommia ulmoides Oliver seeds, has been found to possess anti-inflammatory and antiapoptotic properties. Recent studies have indicated that inflammation, oxidative stress, and apoptosis are involved in the pathophysiology of lipopolysaccharide (LPS)-induced cardiac dysfunction. Our study aimed to investigate the effect of AUB on LPS-induced acute cardiac injury. Male C57BL/6 mice were injected with LPS (one 6 mg/kg injection) to induce cardiac dysfunction without or with AUB pretreatment (20 or 80 mg/kg per day) for 1 week. We found that AUB ameliorated cardiac dysfunction, inflammation, oxidative stress, and apoptosis induced by LPS stimulation. Mechanistically, AUB inhibited LPS-induced oxidative stress by decreasing reactive oxygen species and thioredoxin interaction protein (TXNIP) levels. Moreover, AUB suppressed LPS-induced inflammation and apoptosis by reducing nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)/apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)/caspase-1 inflammasome formation. Overexpression of NLRP3 in cardiomyocytes attenuated the protective effects of AUB. Interestingly, NLRP3 deficiency ameliorated cardiac function and reduced the inflammatory response and oxidative stress after LPS insult in mice, whereas AUB could not further prevent LPS-induced cardiac dysfunction in NLRP3-deficient mice. In summary, AUB exerts a protective effect against LPS-induced inflammation, oxidative stress, and apoptosis in vivo and in vitro by regulating the TXNIP pathway and inactivating the NLRP3/ASC/caspase-1 inflammasome. Hence, AUB may be a promising agent against LPS-induced cardiac dysfunction.SIGNIFICANCE STATEMENT Aucubin exerts a protective effect against lipopolysaccharide-induced cardiac dysfunction by regulating nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome.