Qingping Xiong1, Zhuan Yan2, Jian Liang3, Jun Yuan3, Xueling Chen3, Li Zhou4, Youdong Hu5, Jun Wu3, Yi Jing3, Qianghua Zhang3, Hailun Li6, Yingying Shi3. 1. Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an 223003, Jiangsu, PR China. Electronic address: qpxiong@gmail.com. 2. Department of Emergency, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu, PR China. 3. Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an 223003, Jiangsu, PR China. 4. Department of Intensive Care Unit, Dazhou Central Hospital, Dazhou 635000, Sichuan, China. 5. Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an 223002, Jiangsu, PR China. 6. Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an 223002, Jiangsu, PR China. Electronic address: lihailun101@sina.com.
Abstract
BACKGROUND: Polydatin has been reported to possess remarkable anti-atherosclerotic activities. However, there are different opinions on its regulatory mechanisms. It remains unclear whether the anti-atherosclerotic mechanism of polydatin is related to its autophagic restoration or not. The aim of this study was to explore the question. METHODS: Using atherosclerotic model induced by high-fat diet in apolipoprotein E-deficient mice, the investigation was performed with polydatin alone or in combination with autophagic inhibitor or inducer intervention. Inhibitory sites of polydatin to PI3K were identified by molecular docking. RESULTS: Polydatin can significantly inhibit PI3K/Akt/mTOR pathway proteins expression, improve autophagic dysfunction and reduce atherosclerotic lesions. These effects could be antagonized and reinforced by adding autophagic inhibitor and inducer, respectively. Inhibitory sites of polydatin to PI3K were found to be ASP-810, SER-854, VAL-851, LEU-807, SER-774, LYS-802, ASP-933, SER-919, ASN-920, PHE-930, MEF-922, GLN-859 of PI3Kα. CONCLUSIONS: The mechanism of polydatin to alleviate atherosclerotic lesions was achieved by autophagic restoration.
BACKGROUND:Polydatin has been reported to possess remarkable anti-atherosclerotic activities. However, there are different opinions on its regulatory mechanisms. It remains unclear whether the anti-atherosclerotic mechanism of polydatin is related to its autophagic restoration or not. The aim of this study was to explore the question. METHODS: Using atherosclerotic model induced by high-fat diet in apolipoprotein E-deficient mice, the investigation was performed with polydatin alone or in combination with autophagic inhibitor or inducer intervention. Inhibitory sites of polydatin to PI3K were identified by molecular docking. RESULTS:Polydatin can significantly inhibit PI3K/Akt/mTOR pathway proteins expression, improve autophagic dysfunction and reduce atherosclerotic lesions. These effects could be antagonized and reinforced by adding autophagic inhibitor and inducer, respectively. Inhibitory sites of polydatin to PI3K were found to be ASP-810, SER-854, VAL-851, LEU-807, SER-774, LYS-802, ASP-933, SER-919, ASN-920, PHE-930, MEF-922, GLN-859 of PI3Kα. CONCLUSIONS: The mechanism of polydatin to alleviate atherosclerotic lesions was achieved by autophagic restoration.