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

Deng, Jie; Huang, Min; Wu, Hao

doi:10.1080/21655979.2021.1985299

Cited by 19 publications

(14 citation statements)

References 22 publications

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“…The cAMP, acts a second messenger, plays an important role in a large amount of cellular functions by activating the protein kinase depended on it, which transduces the signal by phosphorylating different target proteins [38, 39]. The deficiency of PRKAR2A , also known as PRKAR2 or PRK2 , has been reported to promote hematopoietic malignancies in vivo 13 and protect mice from experimental colitis by increasing IFN‐stimulated gene expression and modulating the intestinal microbiota, 14 these results suggest that PRKAR2 is critical for tissue development, the process of which is similar with that of CSC progression. In this study, we did not detect the downstream effectors of PRKAR2 in CRC cells and effects of TDRG1 on hematopoietic system and tissue development, which also needs to be explored in the future.…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNATDRG1 aggravates colorectal cancer stemness by binding with miR‐873‐5p to upregulate PRKAR2

Hong

Mai

et al. 2022

Environmental Toxicology

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The effects of long non‐coding RNA TDRG1 have been established in several tumors; however, its roles in colorectal cancer (CRC) progression are never been found. Here, we found that TDRG1 level was upregulated in CRC cells compared to that in normal colon epithelial cells. Additionally, TDRG1 level was remarkably upregulated in 3D non‐adherent spheres derived from the parental CRC cells. Further in vitro and in vivo revealed that TDRG1 knockdown suppressed the stemness of CRC cells. What's more, combined with bioinformatics analysis, luciferase reporter and RNA pull down experiments showed that TDRG1 could bind to miR‐873‐5p, downregulated its level and thus increase the expression of PRKAR2. Finally, it was shown that TDRG1 functioned through the miR‐873‐5p/PRKAR2 axis. This study demonstrated a novel TDRG1/miR‐873‐5p/PRKAR2 signaling in CRC progression.

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Section: Discussionmentioning

confidence: 99%

Long non‐coding RNATDRG1 aggravates colorectal cancer stemness by binding with miR‐873‐5p to upregulate PRKAR2

Hong

Mai

et al. 2022

Environmental Toxicology

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“…Rats in Group 5 were treated with Limonin (40 mg/kg, p.o.,) for 4 days). 10 , 14 On 13 days, the animals were euthanized by CO 2 asphyxiation. Blood was collected via cardiac puncture.…”

Section: Methodsmentioning

confidence: 99%

Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway

Jia

Zhao

Liu

et al. 2023

Immunity Inflam & Disease

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Background Nonsteroidal anti‐inflammatory drugs (NSAIDs) can cause intestinal damage and ulcers and the incidence is increasing. Limonin plays an important role in the regulation of inflammatory diseases, but it has not been reported in the treatment of intestinal injury and ulcers. Methods Indomethacin (INDO) induced intestinal injury and ulcer model in rats. The indexes related to intestinal injury were detected. Western blot and molecular docking techniques were used to detect the docking between Limonin and Nrf2. Next, ML385, an inhibitor of Nrf2/ARE signaling pathway, was applied to treat intestinal epithelial IEC‐6 cells induced by INDO. And CCK8, Western blot, TUNEL, ELISA, DCFH‐DA assay, kits, and immunofluorescence were conducted to detect cell activity, apoptosis, inflammatory response, oxidative stress, and tight junction again. Results INDO can significantly induce intestinal ulcerative lesions in rats. Limonin could improve intestinal ulcerative lesions induced by INDO in rats. Limonin could reduce INDO‐induced inflammatory response and oxidative stress in the small intestine of rats, and improve the intestinal barrier dysfunction induced by INDO. Limonin could dock with Nrf2 structure and activate Nrf2/ARE signaling pathway. ML385 could reverse the protective effect of Limonin against INDO‐induced cell damage. Conclusion Limonin ameliorates INDO‐induced intestinal damage and ulcers through Nrf2/ARE pathway.

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“…Based on some previous reports [ 34 , 36 ], RIPA reagents (Invitrogen) were used to obtain total protein from the murine heart tissue. The protein concentrations were normalized to a consistent level.…”

Section: Methodsmentioning

confidence: 99%

Bone morphogenetic protein 10 alleviates doxorubicin-induced cardiac injury via signal transducer and activator of transcription 3 signaling pathway

Fan

Guo

et al. 2022

Bioengineered

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Doxorubicin (DOX) has limited antitumor applications owing to its association with life-threatening cardiac injury. Oxidative damage and cardiac apoptosis are crucial in DOX-induced cardiac injury. Bone morphogenetic protein 10 (BMP10) is predominantly distributed in the heart and acts as a cardioprotective factor that preserves cardiac function. However, the role of BMP10 in DOX-induced cardiac injury has not yet been explored. The current study aimed to examine the function and mechanism of action of BMP10 in DOX-induced cardiac injury. An adeno-associated viral system was used for the overexpression or silencing of cardiac-specific BMP10, and subsequently, a single dose of DOX was intraperitoneally injected to induce cardiac injury. Results showed that DOX exposure decreased BMP10 expression in the heart. Cardiac-specific overexpression of BMP10 alleviated the oxidative stress and apoptosis and improved cardiac function. Conversely, cardiac-specific silencing of BMP10 aggravated the redox disorder and apoptosis and worsened the cardiac dysfunction caused by DOX. Exogenous BMP10 supplementation amelioratesd the DOX-induced cardiac contractile dysfunction. Mechanistically, we found that phosphorylation of signal transducer and activator of transcription 3 (STAT3) is reduced in DOX-induced cardiotoxicity, and, BMP10 activated impaired STAT3 via a non-canonical pathway. BMP10 lost its cardioprotective function in cardiomyocyte-specific STAT3 knockout (STAT3-cKO) mice. Based on our findings, we suggested that BMP10 is a potential therapeutic agent against DOX-induced cardiac injury and that the cardioprotective effects of BMP10 are dependent on the activation of STAT3.

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

Cited by 19 publications

References 22 publications

Long non‐coding RNATDRG1 aggravates colorectal cancer stemness by binding with miR‐873‐5p to upregulate PRKAR2

Long non‐coding RNATDRG1 aggravates colorectal cancer stemness by binding with miR‐873‐5p to upregulate PRKAR2

Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway

Bone morphogenetic protein 10 alleviates doxorubicin-induced cardiac injury via signal transducer and activator of transcription 3 signaling pathway

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