The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus

Zhang, Yong; Li, Xiaoguang; Li, Jiamin; Zhang, Qingwei; Chen, Xiaohui; Liu, Xin; Zhang, Yue; Zhang, Haiying; Yang, Huan; Hu, Yingying; Wu, Xianxian; Li, Xin; Ju, Jiaming; Yang, Baofeng

doi:10.1038/srep34284

Cited by 19 publications

(9 citation statements)

References 55 publications

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“…β-catenin is an intracellular regulatory transducer that is an important target of the Wnt signaling pathways. GSK-3β regulates β-catenin by regulating its nuclear accumulation, and through this pathway, GSK-3β regulates cell bio-functions, such as gene expression, protein synthesis, and cell viability 60 , 61 . As a result, to further explore the molecular mechanism and the relative signaling pathway, we studied the GSK-3β/β-catenin/Cyclin D1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound promotes Schwann cell viability and proliferation via the GSK-3β/β-catenin signaling pathway

Ren¹,

Chen²,

Du³

et al. 2018

Int. J. Biol. Sci.

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Background: It has been reported that ultrasound enhances peripheral nerve regeneration, but the mechanism remains elusive. Low-intensity pulsed ultrasound (LIPUS) has been reported to enhance proliferation and alter protein production in various types of cells. In this study, we detected the effects of LIPUS on Schwann cells.Material and methods: Schwann cells were separated from new natal Sprague-Dawley rat sciatic nerves and were cultured and purified. The Schwann cells were treated by LIPUS for 10 minutes every day, with an intensity of 27.37 mW/cm2. After treatment for 5 days, MTT, EdU staining, and flow cytometry were performed to examine cell viability and proliferation. Neurotrophic factors, including FGF, NGF, BDNF, and GDNF, were measured by western blot and real-time PCR. GSK-3β, p-GSK-3β, β-catenin and Cyclin D1 protein levels were detected using a western blot analysis. The expression of Cyclin D1 was also detected by immunofluorescence.Results: MTT and EdU staining showed that LIPUS increased the Schwann cells viability and proliferation. Compared to the control group, LIPUS increased the expression of growth factors and neurotrophic factors, including FGF, NGF, BDNF, GDNF, and Cyclin D1. Meanwhile, GSK-3β activity was inhibited in the LIPUS group as demonstrated by the increased level of p-GSK-3β and the ratio of the p-GSK-3β/GSK-3β level. The mRNA and protein expressions of β-catenin were increased in the LIPUS group. However, SB216763, a GSK-3β inhibitor, reversed the effects of LIPUS on Schwann cells.Conclusion: LIPUS promotes Schwann cell viability and proliferation by increasing Cyclin D1 expression via enhancing the GSK-3β/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound promotes Schwann cell viability and proliferation via the GSK-3β/β-catenin signaling pathway

Ren¹,

Chen²,

Du³

et al. 2018

Int. J. Biol. Sci.

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“…Total protein was extracted from endothelial cells using the same procedures as described in detail elsewhere 41 . The protein concentrations were determined by BCA Protein Assay kit (Bio-Rad, Mississauga, ON, Canada).…”

Section: Methodsmentioning

confidence: 99%

Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis

et al. 2018

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Cigarette smoking is a major risk factor for atherosclerosis and other cardiovascular diseases. Increasing evidence has demonstrated that nicotine impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms remain obscure. It is known that cell death and inflammation are crucial processes leading to atherosclerosis. We proposed that pyroptosis may be implicated in nicotine-induced atherosclerosis and therefore conducted the present study. We found that nicotine resulted in larger atherosclerotic plaques and secretion of inflammatory cytokines in ApoE−/− mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with nicotine resulted in NLRP3-ASC inflammasome activation and pyroptosis, as evidenced by cleavage of caspase-1, production of downstream interleukin (IL)-1β and IL-18, and elevation of LDH activity and increase of propidium iodide (PI) positive cells, which were all inhibited by caspase-1 inhibitor. Moreover, silencing NLRP3 or ASC by small interfering RNA efficiently suppressed nicotine-induced caspase-1 cleavage, IL-18 and IL-1β production, and pyroptosis in HAECs. Further experiments revealed that the nicotine-NLRP3-ASC-pyroptosis pathway was activated by reactive oxygen species (ROS), since ROS scavenger (N-acetyl-cysteine, NAC) prevented endothelial cell pyroptosis. We conclude that pyroptosis is likely a cellular mechanism for the pro-atherosclerotic property of nicotine and stimulation of ROS to activate NLRP3 inflammasome is a signaling mechanism for nicotine-induced pyroptosis.

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“…Primary cardiomyocytes were treated with 4% buffered paraformaldehyde for 20 min and then blocked with 1% BSA and 0.1% Triton-X for 2 h at room temperature. Next, the cells were treated with a primary antibody against the N terminal of gasdermin D (GSDMD-N) (Bioss, Beijing, China, 1:200) at 4 °C overnight, followed by treatment with a secondary antibody for 1 h at room temperature 22. The nuclei were stained with DAPI (Beyotime, Shanghai, China), and the results were captured using a fluorescence microscope.…”

Section: Methodsmentioning

confidence: 99%

Metformin Inhibits the NLRP3 Inflammasome via AMPK/mTOR-dependent Effects in Diabetic Cardiomyopathy

et al. 2019

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Metformin is a widely used antidiabetic drug for type 2 diabetes that can play a cardioprotective role through multiple pathways. It is a recognized agonist of AMP-activated protein kinase (AMPK) that blocks mitochondrial complex I. The NLRP3 inflammasome has been demonstrated to be activated in diabetic cardiomyopathy (DCM). However, the role of metformin in regulating the NLRP3 signaling pathway in DCM remains unclear. It has been reported that AMPK can inhibit NLRP3 by activating autophagy. The aim of this study was to investigate whether metformin can inhibit the NLRP3 inflammasome by activating the AMPK/mTOR pathway in DCM. In this study, streptozotocin-induced C57BL/6 mice and high glucose-treated primary cardiomyocytes from neonatal mice were treated with metformin or an AMPK inhibitor compound C. Echocardiography, hematoxylin-eosin and Masson staining showed that the function and morphology of the diabetic hearts were improved after metformin treatment, whereas these parameters deteriorated after intervention with an AMPK inhibitor. Immunohistochemical staining, immunofluorescence staining and western blot assays indicated that the expression levels of mTOR, NLRP3, caspase-1, IL-1β and GSDMD-N were decreased in the diabetic model treated with metformin and were reversed after the administration of an AMPK inhibitor in vivo and in vitro . Mechanistically, our results demonstrated that metformin can activate AMPK, thus improving autophagy via inhibiting the mTOR pathway and alleviating pyroptosis in DCM. Thus, we provide novel information for the treatment of DCM.

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The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus

Cited by 19 publications

References 55 publications

Low-intensity pulsed ultrasound promotes Schwann cell viability and proliferation via the GSK-3β/β-catenin signaling pathway

Low-intensity pulsed ultrasound promotes Schwann cell viability and proliferation via the GSK-3β/β-catenin signaling pathway

Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis

Metformin Inhibits the NLRP3 Inflammasome via AMPK/mTOR-dependent Effects in Diabetic Cardiomyopathy

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