{"title":"Rhodiola and Salidroside Attenuate Oxidative Stress-Triggered H9c2 Cardiomyoblast Apoptosis Through IGF1R-Induced ERK1/2 Activation","authors":"I-Ju Ju, Bruce Chi-Kang Tsai, Wei-Wen Kuo, Chia-Hua Kuo, Yueh-Min Lin, Dennis Jine-Yuan Hsieh, Pei-Ying Pai, Shang-En Huang, Shang-Yeh Lu, Shin-Da Lee, Chih-Yang Huang","doi":"10.1002/tox.24372","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. <i>Rhodiola</i>, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from <i>Rhodiola rosea</i>, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of <i>Rhodiola</i> and salidroside against H<sub>2</sub>O<sub>2</sub>-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H<sub>2</sub>O<sub>2</sub> for 4 h, and subsequently treated with <i>Rhodiola</i> or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H<sub>2</sub>O<sub>2</sub> (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with <i>Rhodiola</i> (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H<sub>2</sub>O<sub>2</sub>-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of <i>Rhodiola</i> and salidroside in H9c2 cells against oxidative damage. Our findings suggest that <i>Rhodiola</i> and salidroside possess antioxidative properties that mitigate H<sub>2</sub>O<sub>2</sub>-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose <i>Rhodiola</i> and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.</p>\n </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5150-5161"},"PeriodicalIF":4.4000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/tox.24372","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.
期刊介绍:
The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are:
Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration;
Natural toxins and their impacts;
Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation;
Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard;
Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.