Styrax (Liquidambar orientalis Mill.) promotes mitochondrial function and reduces cardiac damage following myocardial ischemic injury: the role of the AMPK-PGC1α signaling pathway
Author:
Mu Fei12, Zhao Jiaxin1, Zhao Meina1, Lin Rui1, Liu Kedi3, Zhao Shi3, Tao Xingru1, Li Weihong4, Dai Qi4, Xi Miaomiao34ORCID, Tang Haifeng2, Wang Jingwen1ORCID
Affiliation:
1. Department of Pharmacy, Xijing Hospital, Fourth Military Medical University , Xi’an 710032 , China 2. Department of Chinese Materia Medica and Natural Medicines, Fourth Military Medical University , Xi’an 710032 , China 3. TANK Medicinal Biology Institute of Xi’an , Xi’an 710032 , China 4. Department of Pharmacy, Shaanxi University of Chinese Medicine , Xianyang, Shaanxi 712046 , China
Abstract
Abstract
Objectives
To explore the effect of extract of Styrax (ES) on myocardial ischemic injury and its molecular mechanism, indirectly providing a theoretical basis for the development of ES.
Methods
In order to assess the impact of ES treatment on ischemic heart disease, both a left anterior descending ligation-induced myocardial infarction (MI) model and an ischemia/hypoxia (I/H)-induced H9c2 cell injury model have been constructed. Specifically, Sprague–Dawley rats were randomly assigned to the following groups (n = 8) and administered intragastrically once a day for seven consecutive days: Sham group, MI group, ES-L (0.2 g/kg) group, ES-M (0.4 g/kg) group, ES-H (0.8 g/kg) group, and trimetazidine (TMZ, 0.02 g/kg) group. The cardiac functions and biochemical assessment of rats were detected. Then, we validated experimentally the targets and mechanism of ES on these pathological processes in I/H-induced H9c2 cell injury model.
Key findings
These results showed that different doses of ES (0.2 g/kg, 0.4 g/kg, 0.8 g/kg, intragastric) significantly improved myocardial structure and function when compared to the MI group. The results of 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin, and masson staining indicated that ES could significantly reduce infarct size, inhibit myocardium apoptosis, and decrease myocardial fibrosis. Moreover, ES distinctly suppressed the serum levels of lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and creatine kinase-MB (CK-MB), alleviated myocardial mitochondrial morphology, and stimulated adenosine triphosphate (ATP) production, increased the level of succinate dehydrogenase (SDH), complex I and complex V activity. Different doses of ES (5 μg/ml, 10 μg/ml, 20 μg/ml) also improved cardiomyocyte morphology and decreased the apoptosis rate in H9c2 cells that had been exposed to I/H. Furthermore, the results of western blotting and qRT-PCR indicated that ES promoted the expression of proteins and mRNA related to energy metabolism, including phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), peroxisome proliferator activated receptor gamma coactivator 1 alpha (PCG-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM). Mechanically, after the administration of Compound C (dorsomorphin), an AMPK inhibitor, these effects of myocardial protection produced by ES were reversed.
Conclusions
Collectively, these results demonstrated that ES could improve myocardial mitochondrial function and reduce ischemic injury by activating AMPK/PCG-1α signaling pathway, while indicating its potential advantages as a dietary supplement.
Funder
National Natural Science Foundation of China Xijing Hospital
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
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