AUTHOR=Han Xue , Yang Yakun , Zhang Muqing , Chu Xi , Zheng Bin , Liu Chenxu , Xue Yucong , Guan Shengjiang , Sun Shijiang , Jia Qingzhong TITLE=Protective Effects of 6-Gingerol on Cardiotoxicity Induced by Arsenic Trioxide Through AMPK/SIRT1/PGC-1α Signaling Pathway JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.868393 DOI=10.3389/fphar.2022.868393 ISSN=1663-9812 ABSTRACT=

Background and Objective: Arsenic trioxide (As₂O₃) induced cardiotoxicity to limit the clinical applications of the effective anticancer agent. 6-Gingerol (6G) is the main active ingredient of ginger, a food with many health benefits. The present study aims to investigate the potential pharmacological mechanisms of 6G on As₂O₃-induced myocardial injury.

Methods and Results: Fifty KunMing mice were divided into five groups (n = 10) receiving: 1) physiological saline; 2) 6G (20 mg/kg) alone; 3) As₂O₃ (5 mg/kg); 4) 6G (10 mg/kg) and As₂O₃ (5 mg/kg); 5) 6G (20 mg/kg) and As₂O₃ (5 mg/kg). 6G was given orally and As₂O₃ was given intraperitoneally once per day for seven consecutive days. Biochemical, histopathological, transmission electron microscopy, ELISA, and western blotting analyses were then performed. Based on the resultant data, As₂O₃ was found to induce cardiotoxicity in mice. 6G significantly ameliorated As₂O₃-induced heart injury, histopathological changes, oxidative stress, myocardial mitochondrial damage, inflammation, and cardiomyocyte apoptosis, while reversed As₂O₃-induced inhibition of the AMPK/SIRT1/PGC-1α pathway.

Conclusion: Our experimental results reveal that 6G effectively counteracts As₂O₃-induced cardiotoxicity including oxidative stress, inflammation and apoptosis, which might be attributed to its activation action on AMPK/SIRT1/PGC-1α signaling pathway.