Effects of icariside II ameliorates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by activating Akt/NOS/NF-κB signaling

Yang, Lu; Chao-sheng, Peng; Xia, Jian; Zhang, Wenluo; Tian, Li; Tian, Yange; Yang, Xiaobin; Yue-an, Cao

doi:10.3892/mmr.2017.8342

Cited by 10 publications

(7 citation statements)

References 28 publications

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“…A previous study showed that ICS II could attenuate myocardial fibrosis by inhibiting the NF-kB and transforming growth factor-β1/Smad2 signaling pathways ( 8 ). Another study indicated that ICS II ameliorated diabetic cardiomyopathy in streptozotocin-induced diabetic rats ( 9 ). However, the effects of ICS II on hypoxic-induced cardiomyocyte injury remained elusive.…”

Section: Discussionmentioning

confidence: 99%

“…ICS II has been reported to possess anti-inflammatory, antitumor and anti-osteoporotic properties ( 7 ). In recent years, ICS II has been found to exert various cardioprotective effects, such as the alleviation of myocardial fibrosis and diabetic cardiomyopathy ( 8 , 9 ). However, the specific roles and related molecular mechanisms of ICS II in hypoxia-induced H9c2 cells remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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Icariside II protects cardiomyocytes from hypoxia‑induced injury by upregulating the miR‑7‑5p/BTG2 axis and activating the PI3K/Akt signaling pathway

Wu³

et al. 2020

Int J Mol Med

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Icariside II (ICS II) has been reported to have protective effects against oxidative stress. However, whether ICS II protects cardiomyocytes from myocardial infarction (MI), and the associated underlying mechanisms, remain to be elucidated. Therefore, the current study investigated the effects of ICS II on hypoxia-injured H9c2 cells, as well as the associated molecular mechanisms. A hypoxic injury model was established to emulate the effects of MI. The effects of ICS II on the proliferation of rat cardiomyocyte H9c2 cells were assessed with cell counting kit-8 assays. The apoptotic status of the cells was assessed by flow cytometry, and the expression of apoptosis-related proteins was analyzed by western blotting. A microRNA (miRNA/miR) microarray was used to quantify the differential expression of miRNAs after ICS II treatment, and the levels of miR-7-5p were further quantified by reverse transcription-quantitative PCR. Whether ICS II affected hypoxia-injured cells via miR-7-5p was subsequently examined, and the target of miR-7-5p was also investigated by bioinformatics analysis and luciferase reporter assays. The effects of ICS II on the PI3K/Akt pathway were then evaluated by western blot analysis. Hypoxia treatment decreased viability and the migration and invasion abilities of H9c2 cells, and also induced apoptosis. ICS II significantly increased viability and reduced hypoxia-associated apoptosis. Moreover, ICS II treatment led to the upregulation of miR-7-5p, and the protective effects of ICS II were found to rely on miR-7-5p. Moreover, BTG anti-proliferation factor (BTG2) was identified as a direct target of miR-7-5p, and overexpression of BTG2 inhibited the protective effects of miR-7-5p. Finally, ICS II treatment resulted in the activation of the PI3K/Akt signaling pathway, which is essential for the survival of H9c2 cells under hypoxic conditions. In summary, ICS II reduces hypoxic injury in H9c2 cells via the miR-7-5p/BTG2 axis and activation of the PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Icariside II protects cardiomyocytes from hypoxia‑induced injury by upregulating the miR‑7‑5p/BTG2 axis and activating the PI3K/Akt signaling pathway

Wu³

et al. 2020

Int J Mol Med

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“…For a comprehensive study in DMH it is essential to have a reliable and convenient animal model. STZ, the most widely used chemical to induce diabetes, selectively damages pancreatic cells, causes cell necrosis and results in reduced blood insulin and elevated blood sugar . However, systematic research on the development and examination of cardiac hypertrophy after diabetes onset is scarce.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse

Zhang

Qiu

Huang

et al. 2018

Int J Experimental Path

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Summary The aim of this study was to establish a robust model of diabetic myocardial hypertrophy in Mus musculus castaneus mice. Mice were fed a high‐fat diet for four weeks and then given streptozotocin (STZ, 40 mg kg−1 d−1 for 5 days, intraperitoneally) and fasting blood glucose (FBG) levels were tested after seven days. Mice with FBG levels above 11.1 mmol/L were considered diabetic. Diabetic mice continued to have access to the high‐fat diet until cardiac hypertrophy developed. FBG and body weight (BW) were measured weekly. Myocardial hypertrophy was confirmed by left ventricle (LV) hypertrophy index (LVHI), LV/BW, LV histopathological observation and atrial natriuretic factor (ANF) mRNA expression. Serum insulin and plasma haemoglobin A1c (HbA1c) levels, total cholesterol (TCH) and triglyceride (TG) were measured, and then an insulin resistance index (HOMA.IR) was calculated. The level of FBG in the model group remained above 11.1 mmol/L, and the BW showed significant weight loss, compared with the control group (P < 0.01). The high levels of HbA1c, HOME.IR, TCH and TG, and the low level of insulin suggested that glucose metabolism was not balanced with insulin resistance; meanwhile, higher TCH and TG showed that dyslipidaemia had also developed. After the diabetic mice were kept on the high‐energy diet for another four weeks, histopathological observation showed myocardial injuries, much more surface area and collagen fibres, higher LVHI and LV/BW, and elevated expression of ANF mRNA (P < 0.01), suggesting that myocardial hypertrophy had appeared in Mus musculus castaneus mice under the current experimental conditions. Thus a robust model of diabetic myocardial hypertrophy was established four weeks after confirmation of diabetes, which was induced by feeding a high‐fat diet for four weeks combined with a repeated low‐dose STZ exposure, in Mus musculus castaneus mice.

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“…NF-κB is secreted by vascular endothelium, vascular smooth muscle cells, etc., and is associated with the degradation of IB by utilizing the in ammatory mediators which ultimately stimulate NF-κB, and when NF-κB is activated it can increase to some extent the binding to nuclear DNA, in turn acts on cardiomyocyte behavioral processes and leads to apoptosis [12][13][14]. In addition, NF-κB activates in ammatory cytokines including interleukins and tumor necrosis factor and further circulates to activate NF-κB itself, amplifying the local cascade response in this circulatory pattern and promoting the progression of myocardial injury [15][16][17]. The effects on the NF-B signaling pathway in diabetic cardiomyopathy rats were examined in this work.…”

Section: Discussionmentioning

confidence: 99%

Artemisinin combined with allicin on improving cardiac function, fibrosis, and NF-κB signaling pathway in rats with diabetic cardiomyopathy

Zhang¹,

Wang²

2023

Preprint

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Background This study aimed to see how artemisinin & allicin affected heart function, myocardial fibrosis, and regulating the nuclear factor-B (NF-B) signaling pathways in the myocardial tissue of diabetic cardiomyopathy rats. Methods 50 rats were selected, 10 of which were kept normally without any intervention as the rest 40 were in the normal group injected intraperitoneally 65 µg/g streptozotocin at one time to construct diabetic cardiomyopathy model.37 rats meeting the criteria for successful model establishment were randomly divided into ten rodents in the model category, 9 rats each in the Artemisinin, Allicin, & Combination groups. For four weeks, the Artemisinin group received 75 mg/kg of artemisinin, the Allicin group received 40 mg/kg of allicin, & the combination group received the same doses of artemisinin & allicin gavage as the Artemisinin & Allicin groups. We investigated the cardiac function, myocardial fibrosis, and the aberrant expression of protein levels in NF-κB signaling pathways in each group after the end of the intervention. Results The model group, Artemisinin group, Allicin group, and combination group showed significantly greater cardiac function indexes, including LVEDD, LVESD, LVEF, FS, and E/A with higher expression of NF-B signaling pathway proteins NF-B-p65 and p-NF-B-p65 than the normal group (P < 0.05). LVEDD, LVESD, LVEF, FS, E/A, and NF-B signaling pathway protein NF-B-p65, and p-NF-B-p65 were significantly decreased in the Artemisinin, Allicin, and combination groups when compared with the modeled group (P < 0.05). The combined group had significantly lower expression of LVEDD, LVESD, LVEF, FS, E/A, NF-B signaling pathway protein NF-B-p65, and p-NF-B-p65 than the Artemisinin and Allicin groups (P < 0.05). For comparing the cardiac function indicators LVEDD, LVESD, LVEF, FS, E/A, NF-B signaling pathway protein NF-B-p65, & p-NF-B-p65 expressions, there was no statistical difference here between Artemisinin & Allicin groups (P > 0.05). After observing the myocardial fibrosis in each group, we found the collagen fibers-associated disorder arrangement of the proliferative network in the modeled group, formation of the fibrous scar with large volume, cardiac hypertrophy, inconsistent coloration, nucleus consolidation, disintegration, and even removal. When compared to the model group, the Artemisinin group, Allicin group, & combined group all demonstrated various degrees of improvement in the problematic structure with more intact muscle fibers, neater arrangement, more normal cell morphology, and more homogeneous staining, with the most significant improvement in the combined group. Conclusion Compared with artemisinin and allicin alone, artemisinin combined with allicin improved cardiac dysfunction and reduced myocardial fibrosis in rats with diabetic cardiomyopathy, and both may act via promoting the inactivation of the NF-κB signaling cascade.

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Effects of icariside II ameliorates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by activating Akt/NOS/NF-κB signaling

Cited by 10 publications

References 28 publications

Icariside II protects cardiomyocytes from hypoxia‑induced injury by upregulating the miR‑7‑5p/BTG2 axis and activating the PI3K/Akt signaling pathway

Icariside II protects cardiomyocytes from hypoxia‑induced injury by upregulating the miR‑7‑5p/BTG2 axis and activating the PI3K/Akt signaling pathway

Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse

Artemisinin combined with allicin on improving cardiac function, fibrosis, and NF-κB signaling pathway in rats with diabetic cardiomyopathy

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