Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics.

Pengcheng YU; Jiaru Cao; Huaxin Sun; Yingchao Gong; Hangying Ying; Xinyu Zhou; Yuxing Wang; Chenyang QI; Hang Yang; Qingbo LV; Ling Zhang; Xia Sheng

Return

Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics.

Author: Pengcheng YU ¹ ; Jiaru CAO ² ; Huaxin SUN ² ; Yingchao GONG ¹ ; Hangying YING ¹ ; Xinyu ZHOU ¹ ; Yuxing WANG ¹ ; Chenyang QI ³ ; Hang YANG ² ; Qingbo LV ¹ ; Ling ZHANG ⁴ ; Xia SHENG ⁵
Author Information

1. Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
2. Xinjiang Key Laboratory of Cardiac Electrophysiology and Remodeling, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
3. Department of Cardiology, the First School of Clinical Medicine of Zhejiang Chinese Medicine University, Hangzhou 310006, China.
4. Xinjiang Key Laboratory of Cardiac Electrophysiology and Remodeling, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China. ydzhangling@126.com.
5. Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China. 3101008@zju.edu.cn.
Publication Type:Journal Article
Keywords: Andrographolide; Atrial fibrillation; Network pharmacology; Oxidative stress; Traditional Chinese medicine
MeSH: Animals; Rabbits; Atrial Fibrillation/metabolism*; Kelch-Like ECH-Associated Protein 1/metabolism*; Signal Transduction; NF-E2-Related Factor 2/pharmacology*; Molecular Docking Simulation; Oxidative Stress; Energy Metabolism; Mitochondria/metabolism*; Inflammation/metabolism*; Heme Oxygenase-1
From: Journal of Zhejiang University. Science. B 2023;24(7):632-649
CountryChina
Language:English
Abstract: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.