Aucubin Protects against Myocardial Infarction‐Induced Cardiac Remodeling via nNOS/NO‐Regulated Oxidative Stress

Zheng, Yang; Wu, Qin; Yang, Xiao; Duan, Ming Xia; Liu, Chen; Yuan, Yuan; Meng, Yanyan; Liao, Hai; Tang, Qi‐Zhu

doi:10.1155/2018/4327901

Cited by 27 publications

(19 citation statements)

References 27 publications

(45 reference statements)

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“…Furthermore, AUB suppresses oxidative stress by reducing MDA levels and ROS generation in the context of LPS-induced acute pulmonary injury (Qiu et al, 2018). Our previous study demonstrated that AUB protects against myocardial infarction-induced apoptosis by regulating the neuronal nitric oxide synthase/nitric oxide pathway (Yang et al, 2018). In the present study, AUB was found to alleviate LPS-induced inflammation, oxidative stress, and apoptosis via inhibition of TXNIP and NLRP3 inflammasome.…”

Section: Discussionsupporting

confidence: 56%

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

Duan

Yuan

Liu

et al. 2019

J Pharmacol Exp Ther

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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.

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Section: Discussionsupporting

confidence: 56%

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

Duan

Yuan

Liu

et al. 2019

J Pharmacol Exp Ther

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“…Oxidative stress after MI plays a pathogenic role in post-MI cardiac remodeling [ 3 , 40 ]. Overproduction of ROS following MI may lead to disruption in cell membrane integrity and increased permeability that causes leakage of intracellular enzymes, and necrosis and invasion of extracellular harmful substances into intracellular space [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moderate ROS also upregulated Trx1 and Smyd1 in H9C2 cells, similar to what we found in intact hearts following exercise training. Despite excessive oxidative stress after MI being a contributing factor for cardiac remodeling [ 3 , 40 ], due to its action to increase cell permeability and trigger cell injury signaling pathways [ 41 ], ROS may also induce cardiac angiogenesis [ 58 ] and cardioprotection [ 59 , 60 ] in a dose-dependent manner. Indeed, here, we found that 50-200 µmol/L H 2 O 2 increased Trx1 expression and 300 µmol/L H 2 O 2 led to cell death.…”

Section: Discussionmentioning

confidence: 99%

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Liang

Cai

Zhang

et al. 2020

IJMS

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Pathological remodeling is the main detrimental complication after myocardial infarction (MI). Overproduction of reactive oxygen species (ROS) in infarcted myocardium may contribute to this process. Adequate exercise training after MI may reduce oxidative stress-induced cardiac tissue damage and remodeling. SET and MYND domain containing 1 (Smyd1) is a muscle-specific histone methyltransferase which is upregulated by resistance training, may strengthen sarcomere assembly and myofiber folding, and may promote skeletal muscles growth and hypertrophy. However, it remains elusive if Smyd1 has similar functions in post-MI cardiac muscle and participates in exercise-induced cardioprotection. Accordingly, we investigated the effects of interval treadmill exercise on cardiac function, ROS generation, Smyd1 expression, and sarcomere assembly of F-actin in normal and infarcted hearts. Adult male rats were randomly divided into five groups (n = 10/group): control (C), exercise alone (EX), sham-operated (S), MI induced by permanent ligation of left anterior descending coronary artery (MI), and MI with interval exercise training (MI + EX). Exercise training significantly improved post-MI cardiac function and sarcomere assembly of F-actin. The cardioprotective effects were associated with increased Smyd1, Trx1, cTnI, and α-actinin expression as well as upregulated ratio of phosphorylated AMP-activated protein kinase (AMPK)/AMPK, whereas Hsp90, MuRF1, brain natriuretic peptide (BNP) expression, ROS generation, and myocardial fibrosis were attenuated. The improved post-MI cardiac function was associated with increased Smyd1 expression. In cultured H9C2 cardiomyoblasts, in vitro treatment with H2O2 (50 µmol/L) or AMP-activated protein kinase (AMPK) agonist (AICAR, 1 mmol/L) or their combination for 4 h simulated the effects of exercise on levels of ROS and Smyd1. In conclusion, we demonstrated a novel role of Smyd1 in association with post-MI exercise-induced cardioprotection. The moderate level of ROS-induced upregulation of Smyd1 may be an important target for modulating post-MI cardiac function and remodeling.

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“…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 ]. Meanwhile, geniposide has been revealed protecting against obesity-related cardiac injury through AMPKα- and sirtuin (Sirt1)-dependent mechanisms, etc.…”

Section: Biological Activities Of E Ulmoidesmentioning

confidence: 99%

Traditional application and modern pharmacological research of Eucommia ulmoides Oliv.

et al. 2021

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As a Traditional Chinese Medicine, Eucommia ulmoides Oliv. has been used for the treatment of various diseases since ancient times, involving lumbar pain, knee pain, osteoporosis, hepatoprotection, paralysis, intestinal haemorrhoids, vaginal bleeding, abortion, spermatorrhoea, foot fungus, anti-aging etc. With the developing discovery of E. ulmoides extracts and its active components in various pharmacological activities, E. ulmoides has gained more and more attention. Up to now, E. ulmoides has been revealed to show remarkable therapeutic effects on hypertension, hyperglycemia, diabetes, obesity, osteoporosis, Parkinson’s disease, Alzheimer’s disease, sexual dysfunction. E. ulmoides has also been reported to possess antioxidant, anti-inflammatory, neuroprotective, anti-fatigue, anti-aging, anti-cancer and immunoregulation activities etc. Along these lines, this review summarizes the traditional application and modern pharmacological research of E. ulmoides, providing novel insights of E. ulmoides in the treatment of various diseases.

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Aucubin Protects against Myocardial Infarction‐Induced Cardiac Remodeling via nNOS/NO‐Regulated Oxidative Stress

Cited by 27 publications

References 27 publications

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

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

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Traditional application and modern pharmacological research of Eucommia ulmoides Oliv.

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