Andrographolide Attenuates Myocardial Ischemia-Reperfusion Injury in Mice by Up-Regulating PPAR-α.

Autor: Zhang S; Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China., Ye Y; Department of Ultrasound, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China., Li Q; Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China., Zhao J; Department of Cardiology, Tongzhou People's Hospital, 999 Jianshe Road, Nantong, 226300, Jiangsu Province, China., Song R; Department of Emergency and Critical Care Medicine, Tongzhou People's Hospital, 999 Jianshe Road, Nantong, 226300, Jiangsu Province, China., Huang C; Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, Jiangsu Province, China., Lu X; Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, Jiangsu Province, China., Huang C; Department of Vascular Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. huangchen132@sina.com., Yin L; Department of Cardiology, Tongzhou People's Hospital, 999 Jianshe Road, Nantong, 226300, Jiangsu Province, China. 47973873@qq.con., You Q; Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. yqsyy@ntu.edu.cn.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2024 Nov 25. Date of Electronic Publication: 2024 Nov 25.
DOI: 10.1007/s10753-024-02193-1
Abstrakt: Andrographolide (AGP), a bioactive diterpene lactone, is an active constituent extracted from Andrographis paniculata. It has many biological activities, such as antioxidant, antitumor, antivirus, anti-inflammation, hepatoprotection, and cardioprotection. The aim of the present study is to investigate the cardioprotective effects of AGP in a mouse model of myocardial ischemia-reperfusion injury (MIRI). Adult male C57BL/6 J mice were pre-treated orally with AGP (25 mg/kg) for six days. After 30 min of the left anterior descending coronary artery occlusion followed by 24 h of reperfusion, mice received an additional dose of AGP. The results showed that: (i) AGP pretreatment significantly reduced myocardial infarct size and cardiac injury biomarkers in MIRI mice and improved left ventricular ejection fraction (EF) and fractional shortening (FS); (ii) AGP pretreatment attenuated MIRI-induced oxidative stress imbalance in MIRI mice by increasing total antioxidant capacity (T-AOC) and reducing the levels of hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), malondialdehyde (MDA), and dihydroethidium (DHE); (iii) AGP pretreatment increased Bcl-2 expression and decreased caspase-3 and Bax expression in ischemic myocardial tissue, along with a reduction in TUNEL-positive cells. Further analysis showed that stimulation by I/R decreased peroxisome proliferator-activated receptor-α (PPAR-α) expression in ischemic cardiac tissue, which was prevented by AGP administration. Moreover, administration of the PPAR-α antagonist GW6471 (1 mg/kg) abolished the protective effect of AGP on oxidative stress and apoptosis in the ischemic heart tissue of mice stimulated by ischemia-reperfusion. Taken together, these results suggest that AGP attenuates MIRI-induced cardiac injury by up-regulating PPAR-α expression, thereby preventing oxidative stress and cellular apoptosis.
Competing Interests: Declarations. Competing Interest: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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