Ginsenoside Re Improves Isoproterenol-Induced Myocardial Fibrosis and Heart Failure in Rats

Wang, Quan-wei; Yu, Xiaofeng; Xu, Huali; Zhao, Xin

doi:10.1155/2019/3714508

Cited by 49 publications

(48 citation statements)

References 26 publications

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“…In addition, we have determined a tendency to change in heart shape from ellipsoidal to globular and decrease CT : MT. These findings are in consistent with studies showing that oxidative stress contributes to the 1.4 times decrease of heart weight index, change of heart geometry and development of its fibrosis (Angsutararux et al, 2015;Wang et al, 2019). Our histological findings indicate that the high risk of fibrosis under the influence of doxorubicin is caused by destructive-dystrophic changes in the left atrium and ventricle.…”

Section: Discussionsupporting

confidence: 92%

“…At present, there are no specific clinical practice guidelines for the management of doxorubicin-induced cardiomyopathy. Overall, available cardioprotective measures include a combination of natural antioxidants, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers, diuretics, nitrates, and hydralazine (Wang et al, 2019;Wenningmann et al, 2019). Among those, antioxidants, ACE-inhibitors and beta-blockers showed the best cardioprotective results in patients under doxorubicin treatment (Curigliano et al, 2012;Kamel et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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Impact of corvitin and alpha-ketoglutarate on heart morphology, expression and activity of matrix metalloproteinases 2/9 in the heart of rats with doxorubicin-induced cardiomyopathy

Gordiienko

Poslavska

Шевцова

2019

Regul. Mech. Biosyst.

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The anthracycline anticancer drug doxorubicin is an effective and frequently used chemotherapeutic agent for various malignancies but it causes acute ventricular dysfunction, and also induces cardiomyopathy and heart failure. One of the mechanisms of cardiotoxicity of doxorubicin is oxidative stress, which stimulates myocardial remodeling. Matrix metalloproteinases MMP2 and MMP9 play a key role in this process. Despite extensive research, the expression and activity of these enzymes in the doxorubicin-damaged heart and the effect of antioxidants on these indicators have not been sufficiently studied. The aim of this work was to study the possible cardioprotective effect of the antioxidant drugs corvitin and alpha-ketoglutarate in rats with doxorubicin-induced cardiomyopathy. Cardiomyopathy in rats was induced by intraperitoneal administration of doxorubicin at the dose of 2.5 mg/kg body weight weekly for 28 days. Animals were divided into four groups: group 1 (control) received saline injections (2.5 mL/kg); group 2 – injections of doxorubicin, 3 – corvitin (5 mg/kg) 60 minutes before doxorubicin administration, 4 – doxorubicin and 1% solution of alpha-ketoglutarate in drinking water ad libitum. Heart weight and shape indexes, the ratio of muscle to connective tissues, and heart histology were examined 7 days after the end of drug administration. Activity of MMP2 and MMP9, their intracellular distribution in myocardial tissues were evaluated by gelatin-zymography and immunohistochemistry. It was found that doxorubicin cardiomyopathy in rats was accompanied by a decrease in heart weight index, adaptive change of heart shape from ellipsoid to globular, increase of connective tissue content. Administration of doxorubicin results in profound lesion of the cardiomyocytes of the atria and ventricle, manifested by excessive cytoplasmic expression of MMP2 and MMP9 and an increase their activity in the heart. Antioxidants corvitin and alpha-ketoglutarate have insufficient regenerative effect on mass and shape indexes of heart however, exhibit potent cardioprotective effect by regulation of expression and activity of MMP2 and MMP9.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Impact of corvitin and alpha-ketoglutarate on heart morphology, expression and activity of matrix metalloproteinases 2/9 in the heart of rats with doxorubicin-induced cardiomyopathy

Gordiienko

Poslavska

Шевцова

2019

Regul. Mech. Biosyst.

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“…Ginsenoside Re is the extract of panax ginseng which exhibited protective effects in neural and systematic inflammations through inhibiting the interaction between LPS and TLR4 in macrophages[35]. It was reported to exert anti-fibrosis effect on cardiac fibrosis through down-regulating the expression of p-Smad3, collagen I and reducing the augmentation of collagen fibers[36]. Apart from fibrosis, ginsenoside Re could alleviate inflammation through inhibiting myeloperoxidase activity[37] and decrease fat accumulation through inhibiting HMGCR and cholesterol biosynthesis[38].…”

Section: Resultsmentioning

confidence: 99%

DrAFC: Drug Repositioning Through Anti-Fibrosis Characteristic

Gao

et al. 2020

Preprint

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16Fibrosis is a key component in the pathogenic mechanism of many diseases. These 17 diseases involving fibrosis may share common mechanisms, therapeutic targets and 18 therefore, common intervention strategies and medicines may be applicable for these 19 diseases. For this reason, deliberately introducing anti-fibrosis characteristics into 20 modelling may lead to more success in drug repositioning. In this study, anti-fibrosis 21 knowledge base was first built by collecting data from multiple resources. Both 22 structural and biological profiles were derived from the knowledge base and used for 23 constructing machine learning models including Structural Profile Prediction Model 24 (SPPM) and Biological Profile Prediction Model (BPPM). Three external public data 25 sets were employed for validation purpose and further exploration of potential 26 repositioning drugs in wider chemical space. The resulting SPPM and BPPM models 27 achieve area under the receiver operating characteristic curve (AUC) of 0.879 and 28 0.972 in the training set, and 0.814 and 0.874 in the testing set. Additionally, our 29 results also demonstrate that substantial amount of multi-targeting natural products 30 possess notable anti-fibrosis characteristics and might serve as encouraging candidates 31 in fibrosis treatment and drug repositioning. To leverage our methodology and 32 findings, we developed repositioning prediction platform, Drug Repositioning based 33 on Anti-Fibrosis Characteristic (Dr AFC) that is freely accessible via 34 https://www.biosino.org/drafc. 35 36

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“…This novel study was framed to assess the possible underlying cardioprotective effect of tangeretin (TAN: two different dose‐50/100 mg) against ISP‐induced myocardial infarction in a rat model by checking heart to body weight index, cardiac infarct size, inflammatory markers, oxidative status, apoptotic markers, histopathological changes as well as the protein expressions of PI3K/Akt signaling pathway. Moreover, ISP was preferred for inducing MI or heart failure as it is a noninvasive and simple, gold standard method to induce MI in an animal model with similar human pathophysiological events (Wang, Yu, Xu, Zhao, & Sui, 2019; Wong, Thanikachalam, & Ramamurthy, 2017). The outcome of this animal experiment demonstrates that pretreatment with TAN (50 or 100) can significantly suppress the elevated cardiac infarct size, levels of inflammatory, apoptotic markers, cardiac marker enzymes along with improved antioxidants.…”

Section: Discussionmentioning

confidence: 99%

A possible underlying mechanism behind the cardioprotective efficacy of tangeretin on isoproterenol triggered cardiotoxicity via modulating PI3K/Akt signaling pathway in a rat model

Zhang

Yang

et al. 2020

J Food Biochem

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This study was aimed to examine the possible underlying cardioprotective efficacy of tangeretin (TAN) in rats exposed to isoproterenol (ISP). Forty male SD rats were separated into four equal groups as the control group, ISP (myocardial infarction; MI group) group rats which were injected intraperitoneally (ip) with 85 mg/kg of ISP. Treatment TAN groups (TAN 50 and TAN 100) rats were orally pretreated with TAN (50 or 100 mg/kg) for 28 days before ISP exposure. Pretreatment with TAN (50/100) significantly reduced (p < .05/0.01) the infarct size, levels of inflammatory markers, cardiac marker enzymes, apoptotic markers along with improved antioxidants. Histo‐morphological results also well‐supported the results of the above biochemical parameters by displaying normal myofibrillar arrangement in TAN pretreated rats. Moreover, the protein expressions of pPI3K and pAkt were considerably elevated in rats administered with TAN. Collectively, TAN pretreatment (especially TAN 100) display better cardioprotective activity against ISP‐induced MI rats. Practical applications Tangeretin (TAN) has been reported to exhibit an array of biological functions including cardioprotective, hepatoprotective, and renoprotective activities. However, the in‐depth mechanism is still lacking, which results in this study. Our results indicate that TAN could effectively reduce cardiac infarct size, inflammatory markers, oxidative stress, apoptotic markers, by modulating (upregulating) the protein expressions of the PI3K/Akt signaling pathway. Thus, demonstrating that TAN could be a strong contender for developing a cardioprotective agent and can recommend along with conventional cardioprotective drugs for abolishing MI‐related complications/symptoms. Nevertheless, further human studies are needed to confirm the above suggestion.

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Ginsenoside Re Improves Isoproterenol-Induced Myocardial Fibrosis and Heart Failure in Rats

Cited by 49 publications

References 26 publications

Impact of corvitin and alpha-ketoglutarate on heart morphology, expression and activity of matrix metalloproteinases 2/9 in the heart of rats with doxorubicin-induced cardiomyopathy

Impact of corvitin and alpha-ketoglutarate on heart morphology, expression and activity of matrix metalloproteinases 2/9 in the heart of rats with doxorubicin-induced cardiomyopathy

DrAFC: Drug Repositioning Through Anti-Fibrosis Characteristic

A possible underlying mechanism behind the cardioprotective efficacy of tangeretin on isoproterenol triggered cardiotoxicity via modulating PI3K/Akt signaling pathway in a rat model

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