Therapeutic effects of higenamine combined with [6]‐gingerol on chronic heart failure induced by doxorubicin via ameliorating mitochondrial function

Wen, Jianxia; Zhang, Lu; Wang, Jian; Wang, Jiabo; Wang, Lifu; Wang, Ruilin; Li, Ruisheng; Liu, Honghong; Wei, Shizhang; Li, Haotian; Zhou, Wenjun; Yan, Zhao

doi:10.1111/jcmm.15041

Cited by 39 publications

(38 citation statements)

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“…However, the cardiotoxic effects of DOX limit its use in cancer patients with irreversible degenerative cardiomyopathy and heart failure. More than half of the elderly patients and children who survive lymphoma and other cancers, respectively, show a high risk of cardiotoxicity after DOX treatment [ 7 ]. Therefore, it is essential to study DOX-induced myocardial injury to increase survival rates and improve the quality of life of patients.…”

Section: Introductionmentioning

confidence: 99%

Orosomucoid 1 Attenuates Doxorubicin‐Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

Cheng

Liú

Xing

et al. 2020

BioMed Research International

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Doxorubicin (DOX) is an effective anticancer drug, but its therapeutic use is limited by its cardiotoxicity. The principal mechanisms of DOX-induced cardiotoxicity are oxidative stress and apoptosis in cardiomyocytes. Orosomucoid 1 (ORM1), an acute-phase protein, plays important roles in inflammation and ischemic stroke; however, the roles and mechanisms of ORM1 in DOX-induced cardiotoxicity remain unknown. Therefore, in the present study, we aimed to investigate the function of ORM1 in cardiomyocytes experiencing DOX-induced oxidative stress and apoptosis. A DOX-induced cardiotoxicity animal model was established in C57BL/6 mice by administering an intraperitoneal injection of DOX (20 mg/kg), and the control group was intraperitoneally injected with the same volume of sterilized saline. The effects were assessed after 7 d. Additionally, H9c2 cells were stimulated with DOX (10 μM) for 24 h. The results showed decreased ORM1 and increased oxidative stress and apoptosis after DOX stimulation in vivo and in vitro. ORM1 overexpression significantly reduced DOX-induced oxidative stress and apoptosis in H9c2 cells. ORM1 significantly increased the expression of nuclear factor-like 2 (Nrf2) and its downstream protein heme oxygenase 1 (HO-1) and reduced the expression of the lipid peroxidation end product 4-hydroxynonenal (4-HNE) and the level of cleaved caspase-3. In addition, Nrf2 silencing reversed the effects of ORM1 on DOX-induced oxidative stress and apoptosis in cardiomyocytes. In conclusion, ORM1 inhibited DOX-induced oxidative stress and apoptosis in cardiomyocytes by regulating the Nrf2/HO-1 pathway, which might provide a new treatment strategy for DOX-induced cardiotoxicity.

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Section: Introductionmentioning

confidence: 99%

Orosomucoid 1 Attenuates Doxorubicin‐Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

Cheng

Liú

Xing

et al. 2020

BioMed Research International

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“…These parameters were comprehensively detected in the current study. Our previous study has shown that HG in combination with [6]-GR can substantially increase the CPT-1 level decreased by DOX, which can relieve cardiomyocyte injury induced by DOX via regulating fatty acid metabolism in the TCA cycle based on cell metabonomics [20]. In the present study, serum metabonomics coupled with integrative pharmacology has further improved our understanding of the therapy of DOX induced CHF with HG/[6]-GR from several pivotal aspects.…”

Section: Discussionmentioning

confidence: 67%

“…All rats were intraperitoneally injected with corresponding drugs once a day for seven consecutive days. It should be noted that CHF rats intraperitoneally injected with 5 mg/kg/d HG and [6]-GR showed a good therapeutic effect in our previous study [20]. Hemodynamic indices were assessed after the nal injection.…”

Section: Animal Handlingmentioning

confidence: 94%

Metabonomics coupled with integrated approach reveals the therapeutic effect of higenamine combined with [6]-gingerol on doxorubicin - induced chronic heart failure in rats

Wen

Niu

et al. 2020

Preprint

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The combination of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) is one of the most typical representatives reflecting the very essence of the theory of Chinese material medica compatibility, which has been used to treat cardiovascular disease for many years. Previously, we demonstrated that ALRP-ZR prevented doxorubicin (DOX)-induced chronic heart failure (CHF) in vivo. However, its active components are still unclear. This study was aimed to investigate the therapeutic effect and potential mechanism of higenamine combined with [6]-gingerol (HG/[6]-GR) against doxorubicin (DOX) - induced chronic heart failure (CHF) in rats. Therapeutic effects of HG/[6]-GR on hemodynamics indices, serum biochemical indicators, histopathology and TUNEL staining of rats were assessed. Moreover, a UHPLC-Q-TOF/MS-based serum metabonomic approach coupled with biochemical assay has been performed to identify the potential mechanisms of HG/[6]-GR on DOX-induced CHF. HG/[6]-GR had effects on promoting of hemodynamic indices, decreasing serum biochemical indicators, and alleviating histological damage of heart tissue. Serum metabonomics analyses indicated that the therapeutic effects of HG and [6]-GR were mainly associated with the regulation of eight metabolites and twelve pathways, which may be responsible for the therapeutic efficacy of HG/[6]-GR. Moreover, the results showed that HG/[6]-GR could substantially regulate the expression level of energy metabolism-related metabolites and pathways. Multivariate statistical analysis has provided new insights for understanding CHF and investigating the therapeutic effects and mechanisms of HG/[6]-GR, which influencing the metabolites related to energy metabolism pathway.

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“…The results showed that HG/ Our previous study has shown that HG in combination with [6]-GR can substantially increase the CPT-1 level decreased by DOX, which can relieve cardiomyocyte injury induced by DOX via regulating fatty acid metabolism in the TCA cycle based on cell metabolomics. [20] In the present study, serum metabolomics coupled with integrative pharmacology has further improved our understanding of the therapy of DOX induced CHF with HG/[6]-GR from several pivotal aspects.…”

Section: Discussionmentioning

confidence: 90%

“…It should be noted that CHF rats intraperitoneally injected with 5 mg/kg/d HG and [6]-GR showed a good therapeutic effect in our previous study. [20] Hemodynamic indices were assessed after the nal injection. All animals were sacri ced to collect serum samples and cardiac tissues for HE staining, TUNEL staining, and metabolomic analysis.…”

Section: Animal Handlingmentioning

confidence: 99%

Metabolomics Coupled with Integrated Approach Reveals the Therapeutic Effect of Higenamine Combined with [6]-Gingerol on Doxorubicin - Induced Chronic Heart Failure in Rats

Wen

et al. 2020

Preprint

Self Cite

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Background The combination of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) is one of the most typical representatives reflecting the very essence of the theory of Chinese material medica compatibility, which has been used to treat cardiovascular disease for many years. Previously, we demonstrated that ALRP-ZR prevented doxorubicin (DOX)-induced chronic heart failure (CHF) in vivo. However, its active components are still unclear. This study was aimed to investigate the therapeutic effect and potential mechanism of higenamine combined with [6]-gingerol (HG/[6]-GR) against doxorubicin (DOX) - induced chronic heart failure (CHF) in rats.Methods Therapeutic effects of HG/[6]-GR on hemodynamics indices, serum biochemical indicators, histopathology and TUNEL staining of rats were assessed. Moreover, a UHPLC-Q-TOF/MS-based serum metabolomic approach coupled with biochemical assay had been performed to identify the potential mechanisms of HG/[6]-GR on DOX-induced CHF. Results HG/[6]-GR had effects on promoting of hemodynamic indices, decreasing serum biochemical indicators, and alleviating histological damage of heart tissue. Serum metabolomics analyses indicated that the therapeutic effects of HG and [6]-GR were mainly associated with the regulation of eight metabolites and twelve pathways, which may be responsible for the therapeutic efficacy of HG/[6]-GR. Moreover, the results showed that HG/[6]-GR could substantially regulate the expression level of energy metabolism-related metabolites and pathways.Conclusions Multivariate statistical analysis has provided new insights for understanding CHF and investigating the therapeutic effects and mechanisms of HG/[6]-GR, which influencing the metabolites related to energy metabolism pathway via metabolomics.

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Therapeutic effects of higenamine combined with [6]‐gingerol on chronic heart failure induced by doxorubicin via ameliorating mitochondrial function

Cited by 39 publications

References 38 publications

Orosomucoid 1 Attenuates Doxorubicin‐Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

Orosomucoid 1 Attenuates Doxorubicin‐Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

Metabonomics coupled with integrated approach reveals the therapeutic effect of higenamine combined with [6]-gingerol on doxorubicin - induced chronic heart failure in rats

Metabolomics Coupled with Integrated Approach Reveals the Therapeutic Effect of Higenamine Combined with [6]-Gingerol on Doxorubicin - Induced Chronic Heart Failure in Rats

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