Indigo Fruits Ingredient, Aucubin, Protects against LPS-Induced Cardiac Dysfunction in Mice

Abstract

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 LPSinduced 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)/apoptosisassociated 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 NLRP3deficient 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 lipopolysaccharideinduced cardiac dysfunction by regulating nucleotide-binding oligomerization domain-like receptor family pyrin domaincontaining 3 inflammasome.

Traditional application and modern pharmacological research of Eucommia ulmoides Oliv.

“…Comparing to E. ulmoides extracts or active fraction groups, the individual active components of E. ulmoides have been more intensively studied in the treatment of cardiac diseases, involving cardiac hypertrophy, cardiac fibrosis and cardiac remodelling etc., and their associated mechanisms over the past year [ 13 – 21 ]. For instance, both in vivo and in vitro , aucubin has been found protecting against pressure overload-induced cardiac remodelling via β3-AR-nNOS cascades and it has been found protecting against myocardial infarction-induced cardiac remodeling via nNOS/NO-regulated oxidative stress [ 19 , 21 ].…”

“…An emerging body of research on the anti-inflammatory activities of the active components of E. ulmoides has been conducted in the last five years. It was demonstrated that Aucubin suppressed LPS-induced inflammation and apoptosis in cardiac dysfunction mice, and protected against LPS-induced acute pulmonary injury through regulating Nrf2 and AMPK pathways both in vitro and in vivo [ 13 , 48 ]. Relatively, geniposide is more extensively utilized to investigate its anti-inflammatory effects and its mechanisms.…”

The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

“…Many articles suggest that TRX is an anti-inflammatory molecule at both intracellular and extracellular levels [141,142]. Conversely, TXNIP has a pro-inflammatory role leading to cardiac, vascular and endothelial dysfunctions [13,19,21,[66][67][68]143,144]. Numerous studies conducted since the 2000s suggest that TXNIP may bind to the NLRP3 inflammasome, which enhances the inflammatory response, as reviewed almost a decade ago [65,[69][70][71][72][73][74][75][76][77][78][79][80][81][82] and summarized in Figure 1.…”

Interleukin-35 pretreatment attenuates lipopolysaccharide-induced heart injury by inhibition of inflammation, apoptosis and fibrosis

“…Lipopolysaccharide (LPS), an important component of Gram-negative bacteria, can induce sepsis and related heart damage (5,6). Inflammatory responses triggered by LPS, as evidenced by overproduction of proinflammatory cytokines (IL-6, IL-1β and TNF-α), are considered one of the major mechanisms underlying LPS-induced heart injury (7).…”