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Aristoyunnolin H attenuates extracellular matrix secretion in cardiac fibroblasts by inhibiting calcium influx

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Abstract

Aristoyunnolin H is a novel aristophyllene sesquiterpenoid isolated from the traditional Chinese medicine Aristolochia yunnanensis Franch. The present research was designed to explore the anti-fibrotic effects of aristoyunnolin H in adult rat cardiac fibroblasts (CFs) stimulated with angiotensin II (Ang II). Western blot analysis data showed that aristoyunnolin H reduced the upregulation of fibronectin (FN), connective tissue growth factor and collagen I(Col I) production induced by Ang II in CFs. By studying the dynamic intracellular changes of Ca2+, we further found that while aristoyunnolin H relieved the calcium influx, it has no effect on intracellular calcium store release. Meanwhile, aristoyunnolin H also inhibited the Ang II-stimulated phosphorylation of Ca2+/calmodulin-dependent protein kinase II. In conclusion, aristoyunnolin H may attenuate extracellular matrix secretion in vitro by inhibiting Ang II-induced calcium signaling.

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Acknowledgments

The authors thank the National Natural Science Foundation of China (No. 81102339), the Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation (2011A060901014) and the Medical Scientific Research Foundation of Guangdong Province (No. A2015220) for providing financial support for this work.

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    Authors and Affiliations

    1. Laboratory of Pharmacology and Toxicology, Guangzhou Higher Education Mega Center, School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Waihuan Road, Guangzhou, 510006, Guangdong, People’s Republic of China

      Shao-rui Chen

    2. Department of Pathogenic Biology, Gannan Medical College, Ganzhou, 341000, Jiangxi, People’s Republic of China

      Wen-ping Zhang

    3. Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou Higher Education Mega Center, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Waihuan Road, Guangzhou, 510006, Guangdong, People’s Republic of China

      Jing-mei Bao, Zhong-bin Cheng & Sheng Yin

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    1. Shao-rui Chen
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    Shao-rui Chen and Wen-ping Zhang equally contributed to this work.

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    Chen, Sr., Zhang, Wp., Bao, Jm. et al. Aristoyunnolin H attenuates extracellular matrix secretion in cardiac fibroblasts by inhibiting calcium influx. Arch. Pharm. Res. 40, 122–130 (2017). https://doi.org/10.1007/s12272-016-0843-4

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