The active components derived from Penthorum chinensePursh protect against oxidative-stress-induced vascular injury via autophagy induction
| Autor: | Alena Cong Ling Qiu, Wu Zeng, Yu Han, Vincent Kam Wai Wong, Xiaolei Sun, Yanzheng He, Chaolin Liu, Betty Yuen Kwan Law, An-Guo Wu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell Oxidative phosphorylation Pharmacology medicine.disease_cause Biochemistry Umbilical vein 03 medical and health sciences Mice 0302 clinical medicine Physiology (medical) medicine Autophagy Human Umbilical Vein Endothelial Cells Animals Receptor chemistry.chemical_classification Reactive oxygen species AMPK Hydrogen Peroxide Vascular System Injuries Oxidative Stress 030104 developmental biology medicine.anatomical_structure chemistry Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Free radical biologymedicine. 146 |
| ISSN: | 1873-4596 |
| Popis: | Oxidative stress-induced damage has been proposed as a major risk factor for cardiovascular disease and is a pathogenic feature of atherosclerosis. Although autophagy was reported to have a protective effect against atherosclerosis, its mechanism for reducing oxidative stress remains un-elucidated. In this study, we have identified 4 novel autophagic compounds from traditional Chinese medicines (TCMs), which activated the AMPK mediated autophagy pathway for the recovery of mitochondrial membrane potential (MMP) to reduce the production of reactive oxygen species (ROS) in Human umbilical vein endothelial cells (HUVECs). In this study, 4 compounds (TA, PG, TB and PG1) identified from Penthorum chinense Pursh (PCP) were demonstrated for the first time to possess binding affinity to HUVECs cell membranes via cell membrane chromatography (CMC) accompanied by UHPLC-TOF-MS analysis, and the 4 identified compounds induce autophagy in HUVECs. Among the 4 autophagic activators identified from PCP, TA (Thonningianin A, Pinocembrin dihydrochalcone-7-O-[3″-O-galloyl-4″,6″-hexahydroxydiphenoyl]-glucoside) is the major chemcial component in PCP, which possesses the most potent autophagy effect via a Ca2+/AMPK-dependent and mTOR-independent pathways. Moreover, TA efficiently reduced the level of ROS in HUVECs induced by H2O2. Additionally, the expression of pro- and cleaved-IL-1β in the aortic artery of ApoE-KO mice were also alleviated at the transcription and post-transcription levels after the administration of TA, which might be correlated to the reduction of oxidative-stress induced inflammasome-related Nod-like receptor protein3 (NLRP3) in the aortic arteries of ApoE-KO mice. This study has pinpointed the novel autophagic role of TA in alleviating the oxidative stress of HUVECs and aortic artery of ApoE-KO mice, and provided insight into the therapeutic application of TA in treatment of atherosclerosis or other cardiovascular diseases. |
| Databáze: | OpenAIRE |
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