Jin Wu, Lijuan Chen, Ying Du, Xue Leng, Dongchao Yuan, Mingqian Yang, Yeyu Zhao, Bin Lv, Lianqun Jia
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引用次数: 0
Abstract
Background: Atherosclerosis (AS) is caused by the endothelium injury associated with oxidative stress. Previous studies have shown that the Phlegm-Eliminating and Stasis- Transforming Decoction (Huayu Qutan Decoction, HYQTD) has mitochondrial protective function. The objective of this research was to explore how HYQTD drug-containing serum (HYQTD-DS) could potentially protect mitochondrial energy production in endothelial cells (ECs) from injury caused by hydrogen peroxide (H2O2)-induced oxidative damage in AS through SIRT1/PGC-1α/ Nrf2 pathway.
Methods: After preparation of containing serum, the cells were divided into various categories, such as control group, H2O2 group (an oxidative damage model), HYQTD group, Selisistat (EX527, a SIRT1 inhibitor) combined with H2O2 group, and EX527 combined with HYQTD group. The evaluation of oxidative stress involved measuring reactive oxygen species (ROS) and malondialdehyde (MDA) generation, as well as Superoxide Dismutase (SOD) activity. Mitochondrial function and ultrastructure were measured by Transmission electron microscopy (TEM), mitochondrial membrane potential (MMP), rate of oxygen consumption (OCR), respiratory chain complex activities, and ATP production. The key proteins and gene levels in the SIRT1/PGC-1α/Nrf2 pathway was quantified by quantitative real-time PCR (RT-PCR) and Western blotting analysis.
Results: We found oxidative stress, mitochondrial damage, and mitochondrial energy disorder in H2O2-induced ECs. However it indicated a marked reversal after pretreated with HYQTD-DS. Mechanistically, EX527 induced increased oxidative stress, worse mitochondrial dysfunction, and less ATP synthesis.
Conclusion: We demonstrated that HYQTD-DS attenuated oxidative stress, improved mitochondrial function, and up-regulated mitochondrial ATP synthesis by activating SIRT1/PGC- 1α/Nrf2 pathway-induced mitochondrial biogenesis and its downstream NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDV2).
期刊介绍:
Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include:
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Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.