AUTHOR=Yu Siyi , Qian Hang , Tian Dawei , Yang Mingming , Li Dongfeng , Xu Hao , Chen Jishun , Yang Jingning , Hao Xincai , Liu Zhixin , Zhong Jixin , Yang Handong , Chen Xinlong , Min Xinwen , Chen Jun 

TITLE=Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1074837

DOI=10.3389/fphar.2023.1074837

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To investigate the effects of Linggui Zhugan Decoction on mitochondrial and oxidative damage in rats with chronic heart failure after myocardial infarction and the related mechanisms.</p><p><bold>Methods:</bold> Chronic heart failure after myocardial infarction was established by coronary artery ligation. Heart failure rats were randomly divided into three groups: Model group (<italic>n</italic> = 11), Linggui Zhugan Decoction group (<italic>n</italic> = 12), and captopril group (<italic>n</italic> = 11). Rats whose coronary arteries were only threaded and not ligated were sham group (<italic>n</italic> = 11). Cardiac function, superoxide dismutase (SOD), malondialdehyde (MDA) contents, soluble growth-stimulating expression factor (ST2), and N-terminal B-type brain natriuretic peptide precursor (NTproBNP) levels were analyzed after treatment. Moreover, the level of mitochondrial membrane potential was detected by JC-1 staining, the ultrastructural of myocardial mitochondria were observed by transmission electron microscopy. The related signal pathway of silent information regulator factor 2-related enzyme 1 (SIRT1), adenylate activated protein kinase (AMPK), phosphorylated adenylate activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor <italic>γ</italic> coactivator 1α (PGC-1α) is an important pathway to regulate mitochondrial energy metabolism, and to initiate mitochondrial biogenesis. The expression level was detected by Western blot and reverse transcription to explore the mechanism of the decoction.</p><p><bold>Results:</bold> Compared with the model rats, Linggui Zhugan Decoction significantly improved cardiac function (<italic>p</italic> &lt; 0.05), reduced MDA production (<italic>p</italic> &lt; 0.01), increased SOD activity (<italic>p</italic> &lt; 0.05), reduced ST-2(<italic>p</italic> &lt; 0.01), and NT-proBNP(<italic>p</italic> &lt; 0.05) levels, increased mitochondrial membrane potential, and improved mitochondria function. In addition, Linggui Zhugan Decoction upregulated the expression of SIRT1, p-AMPK, PGC-1α protein, and mRNA in cardiac myocytes.</p><p><bold>Conclusion:</bold> Linggui Zhugan Decoction can improve the cardiac function of heart failure rats by enhancing myocardial antioxidant capacity and protecting the mitochondrial function, the mechanism is related to activating SIRT1/AMPK/PGC-1α signaling pathway.</p>