8-Formylophiopogonanone B antagonizes doxorubicin-induced cardiotoxicity by suppressing heme oxygenase-1-dependent myocardial inflammation and fibrosis

Qin, Dan; Yue, Rongchuan; Deng, Ping; Wang, Xiaobo; Zheng, Zaiyong; Lv, Mingming; Pu, Jun; Xu, Jiqian; Liang, Yaxuan; Pi, Huifeng; Yu, Zhengping; Hu, Houxiang

doi:10.1016/j.biopha.2021.111779

Cited by 20 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies have demonstrated that excessive inflammation is one of the main features of DOX-induced acute cardiotoxicity [37,47,48]. Inflammatory cells are stimulated and proinflammatory cytokines are released following the administration of DOX, thereby amplifying the inflammatory cascade [48][49][50]. In response to extracellular stimulation, NF-κB P65 triggers the formation of inflammatory cytokines [51].…”

Section: Discussionmentioning

confidence: 99%

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3

Zhang

Fan

Wang

et al. 2023

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Cardiotoxicity linked to doxorubicin (DOX) is primarily caused by inflammation, oxidative stress, and apoptosis. The role of tubeimoside I (TBM) in DOX-induced cardiotoxicity remains ambiguous, despite growing evidence that it could reduce inflammation, oxidative stress, and apoptosis in various diseases. This study was designed to investigate the role of TBM in DOX-induced cardiotoxicity and uncover the underlying mechanisms. H9c2 cell line and C57BL/6 mice were used to construct an in vitro and in vivo model of DOX-induced myocardial injury, respectively. We observed that DOX treatment provoked inflammation, oxidative stress, and cardiomyocyte apoptosis, which were significantly alleviated by TBM administration. Mechanistically, TBM attenuated DOX-induced downregulation of sirtuin 3 (SIRT3), and SIRT3 inhibition abrogated the beneficial effects of TBM both in vitro and in vivo. In conclusion, TBM eased inflammation, oxidative stress, and apoptosis in DOX-induced cardiotoxicity by increasing the expression of SIRT3, suggesting that it holds great promise for treating DOX-induced cardiac injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3

Zhang

Fan

Wang

et al. 2023

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Hmox1, an enzyme degrading hemoglobin, was reported to elevate in murine cardiomyocytes after DOX treatment [ 53 ], which is consistent with our observation that Hmox1 was increased in DOX-treated mice. Moreover, overexpression of Hmox1 was reported to exacerbate cardiomyocyte injury in DOX-treated mice [ 54 ], and inhibition of Hmox1 overexpression was proved to effectively decrease cellular ferrous accumulation and protect against ferroptosis [ 55 ]. In addition, a previous study unraveled that the silence of Hmox1 diminished ROS levels and promoted GPX4 expression, which eliminated Hmox1 mediated ferroptosis in diabetic atherosclerosis [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Sheng-Mai-Yin inhibits doxorubicin-induced ferroptosis and cardiotoxicity through regulation of Hmox1

Meng,

Chen,

Sun

et al. 2023

Aging

View full text Add to dashboard Cite

Doxorubicin (DOX) is a potent chemotherapeutic drug used for treating various cancers. However, its clinical use is limited due to its severe cardiotoxicity, which often results in high mortality rates. Sheng-Mai-Yin (SMY), a Traditional Chinese medicine (TCM) prescription, has been reported to exert a cardioprotective effect in various cardiovascular diseases, including DOX-induced cardiotoxicity (DIC). This study aimed to provide novel insights into the underlying cardioprotective mechanism of SMY. SMY, composed of Codonopsis pilosula (Franch.), Ophiopogon japonicus (Thunb.), and Schisandra chinensis (Turcz.) at a ratio of 3:2:1, was intragastrically administered to male C57BL/6 mice for five days prior to the intraperitoneal injection of mitoTEMPO. One day later, DOX was intraperitoneally injected. Hematoxylin-eosin staining and Sirius red staining were carried out to estimate the pharmacological effect of SMY on cardiotoxicity. Mitochondrial function and ferroptosis biomarkers were also examined. AAV was utilized to overexpress Hmox1 to confirm whether Hmox1-mediated ferroptosis is associated with the cardioprotective effect of SMY on DOX-induced cardiotoxicity. The findings revealed that SMY therapy reduced the number of damaged cardiomyocytes. SMY therapy also reversed the inductions of cardiac MDA, serum MDA, LDH, and CK-MB contents, which dramatically decreased nonheme iron levels. In the meantime, SMY corrected the changes to ferroptosis indices brought on by DOX stimulation. Additionally, Hmox1 overexpression prevented SMY's ability to reverse cardiotoxicity. Our results showed that SMY effectively restrained lipid oxidation, reduced iron overload, and inhibited DOX-induced ferroptosis and cardiotoxicity, possibly via the mediation of Hmox1.

show abstract

“…The expression of HMOX1 is reduced in humans and mice with osteoarthritis, aggravating cartilage damage and bone remodeling [ 32 ]. In addition, HMOX1-dependent myocardial inflammation and fibrosis were closely associated with doxorubicin-induced cardiotoxicity [ 33 ]. However, other studies have found that HMOX1 can inhibit the calcification of human VICs in vitro, and the up-regulation of HMOX1 can relieve oxidative stress and vascular calcification in chronic kidney disease [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

CircRNA/lncRNA–miRNA–mRNA network and gene landscape in calcific aortic valve disease

Zheng¹,

Wen²,

Jiang³

et al. 2023

BMC Genomics

View full text Add to dashboard Cite

Background Calcific aortic valve disease (CAVD) is a common valve disease with an increasing incidence, but no effective drugs as of yet. With the development of sequencing technology, non-coding RNAs have been found to play roles in many diseases as well as CAVD, but no circRNA/lncRNA–miRNA–mRNA interaction axis has been established. Moreover, valve interstitial cells (VICs) and valvular endothelial cells (VECs) play important roles in CAVD, and CAVD differed between leaflet phenotypes and genders. This work aims to explore the mechanism of circRNA/lncRNA–miRNA–mRNA network in CAVD, and perform subgroup analysis on the important characteristics of CAVD, such as key cells, leaflet phenotypes and genders. Results We identified 158 differentially expressed circRNAs (DEcircRNAs), 397 DElncRNAs, 45 DEmiRNAs and 167 DEmRNAs, and constructed a hsa-circ-0073813/hsa-circ-0027587–hsa-miR-525-5p–SPP1/HMOX1/CD28 network in CAVD after qRT-PCR verification. Additionally, 17 differentially expressed genes (DEGs) in VICs, 9 DEGs in VECs, 7 DEGs between different leaflet phenotypes and 24 DEGs between different genders were identified. Enrichment analysis suggested the potentially important pathways in inflammation and fibro-calcification during the pathogenesis of CAVD, and immune cell patterns in CAVD suggest that M0 macrophages and memory B cells memory were significantly increased, and many genes in immune cells were also differently expressed. Conclusions The circRNA/lncRNA–miRNA–mRNA interaction axis constructed in this work and the DEGs identified between different characteristics of CAVD provide a direction for a deeper understanding of CAVD and provide possible diagnostic markers and treatment targets for CAVD in the future.

show abstract

8-Formylophiopogonanone B antagonizes doxorubicin-induced cardiotoxicity by suppressing heme oxygenase-1-dependent myocardial inflammation and fibrosis

Cited by 20 publications

References 33 publications

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3

Sheng-Mai-Yin inhibits doxorubicin-induced ferroptosis and cardiotoxicity through regulation of Hmox1

CircRNA/lncRNA–miRNA–mRNA network and gene landscape in calcific aortic valve disease

Contact Info

Product

Resources

About