Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways

Elblehi, Samar S.; El‐Sayed, Yasser S.; Soliman, Mohamed Mohamed; Shukry, Mustafa

doi:10.3390/ani11030886

Cited by 21 publications

(14 citation statements)

References 124 publications

(175 reference statements)

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“…Based on the TCM theories on CHF therapy [30], the methodology has focused on using native compounds against DOX-induced cardiac toxicity. Previous studies have found that Chinese herbal medicines, date palm pollen extract and liensinine, can alleviate the DOX-induced cardiotoxicity [31,32]. In the present study, the effects of SLJ, a new herbal compound, against DOXinduced CHF and its potential mechanisms were investigated in rats.…”

Section: Discussionmentioning

confidence: 90%

Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis

Sun

Song

Xie

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Application of the anticancer drug doxorubicin (DOX) is restricted due to its adverse, cardiotoxic side effects, which ultimately result in heart failure. Moreover, there are a limited number of chemical agents for the clinical prevention of DOX-induced cardiotoxicity. Based on the theories of traditional Chinese medicine (TCM) on chronic heart failure (CHF), Shenlijia (SLJ), a new TCM compound, has been developed to fulfill multiple functions, including improving cardiac function and inhibiting cardiac fibrosis. In the present study, the protective effects and molecular mechanisms of SLJ on DOX-induced CHF rats were investigated. The CHF rat model was induced by intraperitoneal injection of DOX for six weeks with the cumulative dose of 15 mg/kg. All rats were then randomly divided into the control, CHF, CHF + SLJ (3.0 g/kg per day), and CHF + captopril (3.8 mg/kg per day) groups and treated for further four weeks. Echocardiography and the assessment of hemodynamic parameters were performed to evaluate heart function. A protein chip was applied to identify proteins with diagnostic values that were differentially expressed following SLJ treatment. The data from these investigations showed that SLJ treatment significantly improved cardiac function by increasing the left ventricular ejection fraction, improving the hemodynamic index, and inhibiting interstitial fibrosis. Protein chip analysis revealed that SLJ upregulated MCP-1, MDC, neuropilin-2, TGF-β3, thrombospondin, TIE-2, EG-VEGF/PK1, and TIMP-1/2/3 expressions and downregulated that of MMP-13. In addition, immunohistochemistry and western blot results further confirmed that SLJ promoted TIMP-1/2/3 and inhibited MMP-13 expression. The results of the present study suggest that SLJ was effective against DOX-induced CHF rats and is related to the improvement of heart function and ultrastructure and the inhibition of myocardial fibrosis.

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Section: Discussionmentioning

confidence: 90%

Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis

Sun

Song

Xie

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…inhibited DOX-induced apoptosis of cardiac muscle cells via suppressing JNK signaling pathway [13]; And Samar S Elblehi. et al demonstrated that date palm pollen extract averts DOX-induced cardiomyopathy fibrosis by suppressing apoptosis-targeting Bax/Bcl-2 and caspase-3 signaling pathways [14].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a large number of studies have found potential drugs that can improve the cardiotoxicity of DOX from the resources of traditional Chinese medicine, such as Zaid H Maayah et al showed that resveratrol reduced DOX-induced cardiotoxicity in juvenile rat through inactivating the NLRP3-inflammasome [ 12 ]; Wenna Zhou et al indicated that two alkaloids from hippophae rhamnoides linn. inhibited DOX-induced apoptosis of cardiac muscle cells via suppressing JNK signaling pathway [ 13 ]; Samar S Elblehi et al demonstrated that date palm pollen extract averts DOX-induced cardiomyopathy fibrosis by suppressing apoptosis-targeting Bax/Bcl-2 and caspase-3 signaling pathways [ 14 ]. Limonin and other analogues are the main reasons for the bitterness of citrus fruits, which are generally enriched in citrus fruits, especially in seeds.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of limonin against doxorubicin-induced cardiotoxicity via activating nuclear factor - like 2 and Sirtuin 2 signaling pathways

Deng

Huang

2021

Bioengineered

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The anti-tumor and anti-inflammatory effects of limonin have been established, here, we aim to explore whether limonin can induce protective effects against doxorubicin (DOX)-mediated cardiotoxicity which limits its clinical application. We found that limonin attenuated DOX-mediated cytoxicology of myocardial cell line H9C2 by measuring cell viability and reactive oxygen species (ROS) level.Additionally, limonin ameliorates DOX-induced cardiac injury in rat by examining the activity of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) R I P T concentration, and histopathological changes. Mechanistically, it was shown that limonin partially abrogated the inhibition of Nuclear factor -like 2 and Sirtuin 2 signaling induced by DOX. Furthermore, limonin-mediated protective effects on DOX-mediated cytoxicology of H9C2 were rescued by a Sirt2-specific inhibitor or siRNA against Sirt2. Thus, this work reveals that limonin can suppress DOX-mediated cardiotoxicity through activating Nrf2 and Sirt2 signaling.

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“…Then we explored the mechanisms underlying miR-125b-mediated protective effects on Dox-induced cardiotoxicity. As STARD13 has been widely confirmed to be the critical downstream target of miR-125b, 11,14,18 we wondered whether this miR-125b/STARD13 axis existed in myocardial cells. As shown in Figure 4A,B, STARD13 expression was significantly decreased and increased in H9C2 cells with miR-125b overexpression or inhibition, respectively.…”

Section: Mir-125b Targets Stard13 In H9c2 Cellsmentioning

confidence: 99%

“…Plenty of evidences have indicated the important effects of miR-125b in tumor progression. 11 Furthermore, miR-125b has been shown to be critical for cardiac fibrosis and fibroblast-to-myofibroblast transition, 12 acute myocardial infarction, 13 inflammation, 14 and high-fat dietinduced fat accumulation and insulin resistance. 15 However, the effects of miR-125b in Dox-induced cardiotoxicity are still unclear.…”

Section: Introductionmentioning

confidence: 99%

MiR‐125b enhances doxorubicin‐induced cardiotoxicity by suppressing the nucleus‐cytoplasmic translocation of YAP via targeting STARD13

Jin¹,

Yu²,

Ye³

2021

Environmental Toxicology

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The clinical application of doxorubicin (Dox) is limited due to its cardiotoxicity, while the pathogenesis remains to be fully understood. Recent studies have suggested that microRNA (miRNA) plays an important role in Dox-induced cardiotoxicity. This work aims to investigate the effects of miR-125b in Dox-induced cardiotoxicity. Here, mice model combined with cell line analysis were used, and cell viability assay, detection of reactive oxygen species (ROS), malondialdehyde (MDA) activity, lactate dehydrogenase (LDH) activity, glutathione (GSH) level, glutathione peroxidase (GSH-Px) level, superoxide dismutase (SOD) activity, and histopathological changes were performed to characterize miR-125b effects; real-time quantitative polymerase chain reaction (PCR), luciferase reporter assay, RNA immunoprecipitation, and western blot analysis were subjected to reveal the underlying mechanisms. It was found that miR-125b level was upregulated in myocardial cell line H9C2 treated with Dox and miR-125b overexpression enhanced Dox-induced cytotoxicology of H9C2 cells, while miR-125b inhibition exhibited a protective effect by measuring ROS level and cell viability. In consistent, in vivo experiments with miR-125b agomir or antagomir obtained a consistent result through examining the activity of MDA, LDH, GSH, GSH-Px, SOD, and histopathological changes. Furthermore, we found that miR-125b could target STARD13 and thus suppressed the nucleus-cytoplasmic translocation of yesassociated protein (YAP). Additionally, this STARD13/YAP axis is necessary for miR-125b-mediated regulation on Dox-induced cytotoxicology of H9C2 cells. In conclusion, our study demonstrated that miR-125b could enhance Dox-induced cardiotoxicity through targeting the STARD13/YAP axis.

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Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways

Cited by 21 publications

References 124 publications

Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis

Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis

Protective effect of limonin against doxorubicin-induced cardiotoxicity via activating nuclear factor - like 2 and Sirtuin 2 signaling pathways

MiR‐125b enhances doxorubicin‐induced cardiotoxicity by suppressing the nucleus‐cytoplasmic translocation of YAP via targeting STARD13

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