Cardioprotective Effect of &lt;i&gt;Gynostemma pentaphyllum&lt;/i&gt; against Streptozotocin Induced Cardiac Toxicity in Rats via Alteration of AMPK/Nrf2/HO-1 Pathway

Chen, Fang; Zhang, Huan-Yu; He, Dawei; Rao, Chun-Mei; Xu, Bo

doi:10.5650/jos.ess21281

Cited by 7 publications

(6 citation statements)

References 40 publications

(59 reference statements)

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“…The Nrf2-dependent antioxidant response is a well-known protective mechanism against cardiovascular diseases and insults, including myocardial infarction [49], aortic stenosis [50], streptozotocininduced cardiac toxicity [51], myocardial ischemia reperfusion injury [52], diabetic cardiomyopathy [53], and atherosclerosis [54]. Likewise, several studies reported that during septic cardiomyopathy, Nrf2 activity protects heart function via multiple mechanisms [55][56][57].…”

Section: Discussionmentioning

confidence: 99%

Serine/threonine kinase 3 promotes oxidative stress and mitochondrial damage in septic cardiomyopathy through inducing Kelch-like ECH-associated protein 1 phosphorylation and nuclear factor erythroid 2-related factor 2 degradation

Zhu¹,

Dai²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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Serine/threonine kinases (STK3) is a core component of the Hippo pathway and modulates oxidative stress and inflammatory responses in cardiovascular diseases. However, its potential role in septic cardiomyopathy remains undefined. STK3-mediated phosphorylation of Kelch-like ECH-associated protein 1 (KEAP1) was shown to suppress antioxidant gene transcription controlled by nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages. To explore whether STK3 induces KEAP1-mediated suppression of Nrf2 in septic cardiomyopathy, wild-type and global STK3 knockout (STK3 -/- ) mice were treated with LPS. LPS treatment upregulated cardiac STK3 expression. STK3 deletion attenuated myocardial inflammation and cardiomyocyte death, and improved myocardial structure and function. In LPS-challenged HL-1 cardiomyocytes, shRNA-mediated STK3 knockdown normalized mitochondrial membrane potential and ATP production, attenuated apoptosis, and rescued antioxidant gene expression by preventing Nrf2 downregulation. Co-IP, docking analysis, western blotting, and immunofluorescence assays further showed that STK3 binds and phosphorylates KEAP1, promoting Nrf2 downregulation. Accordingly, transfection of phosphodefective KEAP1 mutant protein in cardiomyocyte restored Nrf2 expression and mitochondrial performance upon LPS, while expression of a phosphomimetic KEAP1 mutant abolished the mitochondria-protective and pro-survival effects of STK3 deletion. These findings suggest that STK3 upregulation contributes to septic cardiomyopathy by phosphorylating KEAP1 to promote Nrf2 degradation and suppression of the antioxidant response.

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Section: Discussionmentioning

confidence: 99%

Serine/threonine kinase 3 promotes oxidative stress and mitochondrial damage in septic cardiomyopathy through inducing Kelch-like ECH-associated protein 1 phosphorylation and nuclear factor erythroid 2-related factor 2 degradation

Zhu¹,

Dai²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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“…Many studies have used STZ to model diabetes cardiomyopathy in rats [ 15 , 16 , 17 ]. In this diabetic cardiomyopathy rat model, elevated ROS levels are presented with higher MDA levels and decreased antioxidant—such as SOD, GPx and Nrf2—expression, which then induced cardiac cell damage [ 1 , 5 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…This can decrease the production of antioxidant enzymes such as SOD, GPx and Catalase. Nfr2 is an essential transcription factor that controls the response of antioxidants for maintenance in homeostasis on cellular redox [ 5 , 12 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…The administration of natural product antioxidants has been proven to decrease oxidative stress. A recent study shows that Nrf2 has a crucial role in the protection of cardiac cell damage and death caused by oxidative stress in diabetic complications [ 5 , 6 , 7 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Overproduction of ROS will activate the process of lipid peroxidation in polyunsaturated fats (PUFA) of the cell membrane that produce lipid peroxides or MDA. High levels of MDA indicate elevated ROS production, which causes cardiac cell damage [ 5 , 6 , 7 ]. MDA can be used to assess ROS in diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

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Protective Mechanism Pathway of Swietenia macrophylla Extract Nanoparticles against Cardiac Cell Damage in Diabetic Rats

2023

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Hyperglycemia causes cardiac cell damage through increasing ROS production during diabetic complications. The current study proves the antioxidant activity of Swietenia macrophylla (S. macrophylla) extract nanoparticles as a protector against streptozotocin (STZ)-induced cardiac cell damage. In this research, high-energy ball milling is used to create S. macrophylla extract nanoparticles. The active chemical compounds in the S. macrophylla extract nanoparticles were analyzed through phytochemical screening and GC-MS. Furthermore, we characterized the size of S. macrophylla extract nanoparticles with Dynamic Light Scattering (DLS). Forty male rats were divided randomly into five groups. In the control group, rats received aqua dest orally; in the diabetic group, rats were injected intraperitoneally with STZ; in the S. macrophylla group, rats were injected with STZ and orally given S. macrophylla extract nanoparticles. The results of phytochemical screening showed that S. macrophylla extract nanoparticles contain saponins, flavonoids, alkaloids, phenolics and tannins. Seven chemical compounds in S. macrophylla extract nanoparticles were identified using GC-MS, including phenol, piperidine, imidazole, hexadecene, heptadecanol, dihexylsulfide and heptanol. DLS showed that the S. macrophylla extract nanoparticles’ size was 91.50 ± 23.06 nm. Injection with STZ significantly increased malondialdehyde (MDA) levels in cardiac tissue and creatine kinase–myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels in serum. STZ also significantly reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in cardiac tissue compared with the control group (p < 0.05). In contrast, the administration of S. macrophylla extract nanoparticles can prevent STZ-induced cardiac cell damage through decreasing the level of CK-MB and LDH in serum and the level of MDA in cardiac tissue. S. macrophylla extract nanoparticles also significantly increased Nrf2 expression as well as SOD and GPx levels in cardiac tissue. These effects are related to the prevention of cardiac histopathological alteration (degeneration and necrosis) in diabetic rats. These results suggest that S. macrophylla nanoparticles contain active compounds such as flavonoids, phenols, piperidine, imidazole and hexadecene and have strong antioxidant activity. These can act as a potential cardioprotective agent against STZ-induced cardiac cell damage due to its antioxidant properties.

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Sinomenine protects against atherosclerosis in apolipoprotein E-knockout mice by inhibiting of inflammatory pathway

Gao,

Yang,

Zeng

et al. 2024

Inflammopharmacol

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Cardioprotective Effect of <i>Gynostemma pentaphyllum</i> against Streptozotocin Induced Cardiac Toxicity in Rats via Alteration of AMPK/Nrf2/HO-1 Pathway

Cited by 7 publications

References 40 publications

Serine/threonine kinase 3 promotes oxidative stress and mitochondrial damage in septic cardiomyopathy through inducing Kelch-like ECH-associated protein 1 phosphorylation and nuclear factor erythroid 2-related factor 2 degradation

Serine/threonine kinase 3 promotes oxidative stress and mitochondrial damage in septic cardiomyopathy through inducing Kelch-like ECH-associated protein 1 phosphorylation and nuclear factor erythroid 2-related factor 2 degradation

Protective Mechanism Pathway of Swietenia macrophylla Extract Nanoparticles against Cardiac Cell Damage in Diabetic Rats

Sinomenine protects against atherosclerosis in apolipoprotein E-knockout mice by inhibiting of inflammatory pathway

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