Cardioprotective effects of ulinastatin against isoproterenol-induced chronic heart failure through the PI3K‑Akt, p38 MAPK and NF-κB pathways

Li, Lin; Hao, Jian; Jiang, Xian Cheng; Li, Ping; Hu, Sen

doi:10.3892/mmr.2017.7934

Cited by 18 publications

(18 citation statements)

References 33 publications

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“…Li et al reported that ulinastatin against ISO-induced chronic heart failure through the PI3 K Akt, p38 MAPK, and NF-kB pathways. 73 In this study, the ZBN treatment prevented the mRNA expression pattern of AKT signaling molecules. Similarly, the ZBN treatment modulates mTOR/PI3K/AKT signaling events in colon cancer cells.…”

Section: Discussionmentioning

confidence: 61%

Anti-inflammatory and anti-apoptotic effect of zingiberene on isoproterenol-induced myocardial infarction in experimental animals

Li¹,

Radhiga

Kanimozhi

et al. 2020

Hum Exp Toxicol

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This study aimed to investigate the antihyperlipidemic and anti-inflammatory effect of zingiberene (ZBN) on isoproterenol-(ISO) induced myocardial infarction in rats. ZBN (10 mg/kg b.wt.) was orally administered to rats for 21 days and ISO (85 mg/kg b.wt.) was subcutaneously injected into the rats at 24 h intervals for the last 2 consecutive days. We observed increased serum creatine kinase, creatine kinase-MB, cardiac troponin T, and I levels in ISO-treated MI rats. Conversely, ZBN oral administration significantly prevented in cardiac marker enzyme activities in ISO-mediated rats. We also noticed that ZBN oral administration prevented ISO-induced expression of lipid peroxidative markers, total cholesterol, triglycerides, phospholipids, free fatty acids, very-low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) to the normal basal level. Furthermore, ZBN restored ISO-mediated antioxidant status, increased level of high-density lipoprotein cholesterol (HDL-C), and tissue phospholipids to the near-normal levels. Besides, ZBN pre-treatment significantly reduced the level of inflammatory markers (TNF-α, IL-6, NF-κB, and IL-1β) in ISO-induced MI in rats. We noticed that ZBN pretreatment inhibited the pro-apoptotic proteins Bax and cytochrome c and increased the Bcl-2 expression in ISO induced rats. The gene expression profiling by qRT-PCR array illustrates that ZBN treatment prevents the ISO mediated activation of cardiac markers, inflammatory, and fibrosis-related genes in the heart tissue. Taken together, pre-treatment with ZBN attenuated ISO-induced MI resolved exhibits the anti-inflammatory and antiapoptotic effect.

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Section: Discussionmentioning

confidence: 61%

Anti-inflammatory and anti-apoptotic effect of zingiberene on isoproterenol-induced myocardial infarction in experimental animals

Li¹,

Radhiga

Kanimozhi

et al. 2020

Hum Exp Toxicol

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“…Furthermore, population‐based studies reiterated that there is a positive association between type 1 diabetes and HF (Miki, Yuda, Kouzu, & Miura, ). ISO treatment induced the cardiac hypertrophy (CH) as evidenced by arrhythmias, myocyte loss, and fibrosis with progression to HF (Li, Hao, Jiang, Li, & Sen, ). The current antidiabetic drugs are less effective and even harmful to patients with DM with HF.…”

Section: Discussionmentioning

confidence: 99%

“…ISO treatment induced the cardiac hypertrophy (CH) as evidenced by arrhythmias, myocyte loss, and fibrosis with progression to HF (Li, Hao, Jiang, Li, & Sen, 2018). The current antidiabetic drugs are less effective and even harmful to patients with DM with HF.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of kaempferol on heart via the regulation of Nrf2, NF‐κβ, and PI3K/Akt/GSK‐3β signaling pathways in isoproterenol‐induced heart failure in diabetic rats

Zhang

Guo

Wang

et al. 2019

Drug Development Research

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This study was designed to delineate the effect of kaempferol (KF) on heart failure (HF) in diabetic rats. Streptozotocin‐induced male diabetic rats received KF orally at 10 and 20 mg/kg for 42 consecutive days. In last 2 days of the experimental period, isoproterenol was subcutaneously injected at 85 mg/kg to induce HF. The hearts were processed for hemodynamic, biochemical, molecular, and histological investigations. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were elevated in KF‐treated HF‐induced diabetic rats. Moreover, KF treatment resulted in decreased fasting blood glucose and glycosylated hemoglobin levels with increased serum insulin levels. Besides, serum cardiac injury markers like troponin‐I, creatine kinase‐muscle/brain, lactate dehydrogenase, and brain natriuretic peptide levels were significantly reduced in KF treatment. KF treatment has shown decrease in cardiac heme oxygenase‐1, nuclear factor erythroid 2–related factor 2 (Nrf‐2), and γ‐glutamylcysteine synthetase with increased Keap1 mRNA levels. The cardioprotection of KF was improved by inhibition of apoptosis via blocking phosphorylation of Akt/glycogen synthase kinase (GSK)‐3β and p38 mitogen‐activated protein‐kinase/extracellular signal‐regulated kinases signaling pathways in HF‐induced diabetic rats. Moreover, reduced cardiac apoptosis in KF treatment was confirmed by decreased terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL) positive cells, histopathological changes in HF‐induced diabetic rats. Therefore, the cardioprotective effect of KF is attributed to the regulation of Nrf2, nuclear factor kappa‐light‐chain‐enhancer of activated B cells, and Akt/GSK‐3β signaling pathways in HF‐induced diabetic rats.

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“…The MAPK signaling pathway is a highly conserved module that is involved in the majority of cellular functions, including cell proliferation, differentiation, and migration. Previous studies have shown that downregulation of the MAPK signaling pathway has a cardioprotective effect against HF (Li et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, high RAAS activity can result in apoptosis, while inhibiting RAAS can prevent apoptosis (Velez Rueda et al, 2012; Kooptiwut et al, 2015). Based on the literature, downregulating the MAPK signaling pathway can have cardioprotective effects against HF (Li et al, 2018), while inhibiting RAAS can abrogate MAPK activation (Lebeche et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

An Integrated System Biology Approach Yields Drug Repositioning Candidates for the Treatment of Heart Failure

Yang

Qin

2019

Front. Genet.

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Identifying effective pharmacological treatments for heart failure (HF) patients remains critically important. Given that the development of drugs de novo is expensive and time consuming, drug repositioning has become an increasingly important branch. In the present study, we propose a two-step drug repositioning pipeline and investigate the novel therapeutic effects of existing drugs approved by the US Food and Drug Administration to discover potential therapeutic drugs for HF. In the first step, we compared the gene expression pattern of HF patients with drug-induced gene expression profiles to obtain preliminary candidates. In the second step, we performed a systems biology approach based on the known protein–protein interaction information and targets of drugs to narrow down preliminary candidates to obtain final candidates. Drug set enrichment analysis and literature search were applied to assess the performance of our repositioning approach. We also constructed a mode of action network for each candidate and performed pathway analysis for each candidate using genes contained in their mode of action network to uncover pathways that potentially reflect the mechanisms of candidates’ therapeutic efficacy to HF. We discovered numerous preliminary candidates, some of which are used in clinical practice and supported by the literature. The final candidates contained nearly all of the preliminary candidates supported by previous studies. Drug set enrichment analysis and literature search support the validity of our repositioning approach. The mode of action network for each candidate not only displayed the underlying mechanisms of drug efficacy but also uncovered potential biomarkers and therapeutic targets for HF. Our two-step drug repositioning approach is efficient to find candidates with potential therapeutic efficiency to HF supported by the literature and might be of particular use in the discovery of novel effective pharmacological therapies for HF.

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Cardioprotective effects of ulinastatin against isoproterenol-induced chronic heart failure through the PI3K‑Akt, p38 MAPK and NF-κB pathways

Cited by 18 publications

References 33 publications

Anti-inflammatory and anti-apoptotic effect of zingiberene on isoproterenol-induced myocardial infarction in experimental animals

Anti-inflammatory and anti-apoptotic effect of zingiberene on isoproterenol-induced myocardial infarction in experimental animals

The protective effect of kaempferol on heart via the regulation of Nrf2, NF‐κβ, and PI3K/Akt/GSK‐3β signaling pathways in isoproterenol‐induced heart failure in diabetic rats

An Integrated System Biology Approach Yields Drug Repositioning Candidates for the Treatment of Heart Failure

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