Naringenin attenuates pressure overload-induced cardiac hypertrophy

Zhang, Ning; Zheng, Yang; Yuan, Yuan; Li, Fangfang; Yuan, Linhong; Ma, Zhen‐Guo; Liao, Hai‐Han; Bian, Zhou‐Yan; Zhang, Yao; Zhou, Haoming; Deng, Wei; Zhou, Mingmei; Tang, Qi‐Zhu

doi:10.3892/etm.2015.2816

Cited by 37 publications

(20 citation statements)

References 26 publications

(27 reference statements)

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“…In addition, naringenin downregulates the release of proinflammatory cytokines such as TNF-α and IL-1β, which abrogated the ischemic brain injury through the suppression of nuclear factor-κB-mediated neuroinflammation ( 22 ). Conversely, it has been proven to attenuate interstitial fibrosis in pressure induced-cardiac hypertrophy via PI3K/Akt, ERK and JNK signaling pathways ( 23 ) and to inhibit renal fibrosis by blocking Smad3 phosphorylation and transcription ( 24 ).…”

Section: Introductionmentioning

confidence: 99%

Naringenin attenuates fibroblast activation and inflammatory response in a mechanical stretch-induced hypertrophic scar mouse model

Shan

Zhang

et al. 2017

Molecular Medicine Reports

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The pathogenesis and therapy of hypertrophic scars (HS) have not yet been established. The aim of the present study was to investigate the potential effect of naringenin on HS and its underlying mechanisms. The mouse model of HS was prepared by a mechanical stretch device and then treated with naringenin at various concentrations. Histological studies were performed to evaluate scar hypertrophy by hematoxylin and eosin, as well as Masson's trichrome staining. The activation of HS fibroblasts was determined based on reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemical staining. Following observing the retention of inflammation cells by immunohistochemistry, the cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and transforming growth factor (TGF)-β1, mRNA and protein levels were quantitated by RT-qPCR, ELISA and western blotting methods. As a result, naringenin significantly inhibited the formation of HS in a concentration-dependent manner. In addition, naringenin inhibited fibroblast activation and inflammatory cell recruitment. In addition, mRNA and protein expression levels of TNF-α, IL-1β, IL-6 and TGF-β1 were downregulated following naringenin treatment. The current study highlighted a new pharmacological activity of naringenin on HS. The mechanism of action of naringenin was associated with the inhibition of fibroblast activation and local inflammation. These results suggested that naringenin may serve as a novel agent for treatment of HS.

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Section: Introductionmentioning

confidence: 99%

Naringenin attenuates fibroblast activation and inflammatory response in a mechanical stretch-induced hypertrophic scar mouse model

Shan

Zhang

et al. 2017

Molecular Medicine Reports

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“…In fact, many researchers have realized the association of mitogen-activated protein kinase (MAPK) involvement during DCM development. MAPK signaling pathways, such as extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, are demonstrated to be actively involved in myocardial dysfunction [9,10], hypertrophy [11,12,13], fibrosis [14,15,16] and heart failure [17,18,19]. As one MAPK family member, ERK1/2 has been known to be involved in cardiac hypertrophy [20,21].…”

Section: Introductionmentioning

confidence: 99%

The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy

Sun

Tong

et al. 2016

IJMS

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Diabetes mellitus is a chronic metabolic condition that affects carbohydrate, lipid and protein metabolism and may impair numerous organs and functions of the organism. Cardiac dysfunction afflicts many patients who experience the oxidative stress of the heart. Diabetic cardiomyopathy (DCM) is one of the major complications that accounts for more than half of diabetes-related morbidity and mortality cases. Chronic hyperglycemia and hyperlipidemia from diabetes mellitus cause cardiac oxidative stress, endothelial dysfunction, impaired cellular calcium handling, mitochondrial dysfunction, metabolic disturbances, and remodeling of the extracellular matrix, which ultimately lead to DCM. Although many studies have explored the mechanisms leading to DCM, the pathophysiology of DCM has not yet been fully clarified. In fact, as a potential mechanism, the associations between DCM development and mitogen-activated protein kinase (MAPK) activation have been the subjects of tremendous interest. Nonetheless, much remains to be investigated, such as tissue- and cell-specific processes of selection of MAPK activation between pro-apoptotic vs. pro-survival fate, as well as their relation with the pathogenesis of diabetes and associated complications. In general, it turns out that MAPK signaling pathways, such as extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, are demonstrated to be actively involved in myocardial dysfunction, hypertrophy, fibrosis and heart failure. As one of MAPK family members, the activation of ERK1/2 has also been known to be involved in cardiac hypertrophy and dysfunction. However, many recent studies have demonstrated that ERK1/2 signaling activation also plays a crucial role in FGF21 signaling and exerts a protective environment of glucose and lipid metabolism, therefore preventing abnormal healing and cardiac dysfunction. The duration, extent, and subcellular compartment of ERK1/2 activation are vital to differential biological effects of ERK1/2. Moreover, many intracellular events, including mitochondrial signaling and protein kinases, manipulate signaling upstream and downstream of MAPK, to influence myocardial survival or death. In this review, we will summarize the roles of ERK1/2 pathways in DCM development by the evidence from current studies and will present novel opinions on “differential influence of ERK1/2 action in cardiac dysfunction, and protection against myocardial ischemia-reperfusion injury”.

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“…Activation of AGE receptor (RAGE) via AGE binding under diabetic conditions activates MAPKs in PC12 and rat pulmonary artery smooth muscle cells . Many researchers have realized the association between MAPK activation and the development of diabetic complications, such as DCMP . For example, activation of these three MAPK signaling pathways is implicated in myocardial dysfunction, hypertrophy, fibrosis, and HF …”

Section: Metallothionein and Its Broad‐spectrum Functionsmentioning

confidence: 99%

“…110,111 Many researchers have realized the association between MAPK activation and the development of diabetic complications, such as DCMP. [112][113][114][115][116][117][118][119][120][121][122] For example, activation of these three MAPK signaling pathways is implicated in myocardial dysfunction, 112,113 hypertrophy, [114][115][116] fibrosis, [117][118][119] and HF. [120][121][122] Although direct evidence of the prevention of diabetes or diabetic complications by MT via inactivation of the three MAPK signaling pathways is lacking, there are several studies showing that by inhibiting MAPK pathways MTs can protect the heart or cardiac cells against the deleterious effects of lipopolysaccharide, 123 arsenic trioxide, 87 and Cd.…”

Section: Classical View: Relieving Os Inflammation Cell Death and mentioning

confidence: 99%

Reappraisal of metallothionein: Clinical implications for patients with diabetes mellitus

Park

Zhang

Cai

2018

Journal of Diabetes

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Reactive oxygen and nitrogen species (ROS and RNS, respectively) are byproducts of cellular physiological processes of the metabolism of intermediary nutrients. Although physiological defense mechanisms readily convert these species into water or urea, an improper balance between their production and removal leads to oxidative stress (OS), which is harmful to cellular components. This OS may result in uncontrolled growth or, ultimately, cell death. In addition, ROS and RNS are closely related to the development of diabetes and its complications. Therefore, numerous researchers have proposed the development of strategies for the removal of ROS/RNS to prevent or treat diabetes and its complications. Some molecules that are synthesized in the body or obtained from food participate in the removal and neutralization of ROS and RNS. Metallothionein, a cysteine-rich protein, is a metal-binding protein that has a wide range of functions in cellular homeostasis and immunity. Metallothionein can be induced by a variety of conditions, including zinc supplementation, and plays a crucial role in mediating anti-OS, anti-apoptotic, detoxification, and anti-inflammatory effects. Metallothionein can modulate various stress-induced signaling pathways (mitogen-activated protein kinase, Wnt, nuclear factor-κB, phosphatidylinositol 3-kinase, sirtuin 1/AMP-activated protein kinase and fibroblast growth factor 21) to alleviate diabetes and diabetic complications. However, a deeper understanding of the functional, biochemical, and molecular characteristics of metallothionein is needed to bring about new opportunities for OS therapy. This review focuses on newly proposed functions of a metallothionein and their implications relevant to diabetes and its complications.

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Naringenin attenuates pressure overload-induced cardiac hypertrophy

Cited by 37 publications

References 26 publications

Naringenin attenuates fibroblast activation and inflammatory response in a mechanical stretch-induced hypertrophic scar mouse model

Naringenin attenuates fibroblast activation and inflammatory response in a mechanical stretch-induced hypertrophic scar mouse model

The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy

Reappraisal of metallothionein: Clinical implications for patients with diabetes mellitus

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