Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation
Open accessAbstract
Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders.
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Punicalagin, by activating AMPK, prevented HFD-related cardiac disorders via modulating mitochondria as well as phase II enzymes.
“These findings collectively elucidated that punicalagin, by activating AMPK, prevented HFD-related cardiac disorders via modulating mitochondria as well as phase II enzymes [142].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [142]
Pomegranate extract activated AMPK, which may be responsible for the intervention of mitochondrial loss through promoting mitochondrial biogenesis and the attenuation of oxidative stress by means of upregulating phase II enzymes in HFD hearts.
“Concomitantly, pomegranate extract activated AMPK, which may be responsible for the intervention of mitochondrial loss through promoting mitochondrial biogenesis and the attenuation of oxidative stress by means of upregulating phase II enzymes in HFD hearts [142].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [142]
Punicalagin protects against HFD-induced cardiac disorders by activating AMPK pathway and promoting mitochondrial biogenesis.
“Punicalagin, the major active component in pomegranate extract, protects against HFD-induced cardiac disorders by activating AMPK pathway and promoting mitochondrial biogenesis [142].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [142]
In Sprague Dawley rats, administration of pomegranate extract, composed of 40% punicalagin, effectively blocked HFD-induced cardiac accumulation of fat and myocardial damage.
“In Sprague Dawley rats, administration of pomegranate extract, composed of 40% punicalagin, effectively blocked HFD-induced cardiac accumulation of fat (e.g., cholesterol and triglycerides) and myocardial damage [142].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [142]
Punicalagin was the main component of pomegranate extract that specifically activated AMPK in cardiomyocytes via quickly reducing the intracellular ATP-to-ADP ratio.
“Cell culture study demonstrated that punicalagin was the main component of pomegranate extract that specifically activated AMPK in cardiomyocytes via quickly reducing the intracellular ATP-to-ADP ratio [142].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [142]
Punicalagin stimulates mitochondrial biogenesis in cardiomyocytes from obese rats.
“Punicalagin, the most abundant ellagitannin in the pomegranate fruit, stimulates mitochondrial biogenesis in cardiomyocytes from obese rats233.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [233]
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- Authors
- Cao, K., Xu, J., Pu, W., Dong, Z., Sun, L., Zang, W., Gao, F., Zhang, Y., Feng, Z., & Liu, J.
- Affiliations
- Xi'an Jiaotong University (CN)
- Nestlé (China) (CN)
- Air Force Medical University (CN)
- Tianjin University of Sport (CN)
- Corresponding author
- Feng, Zhihui
- Liu, Jiankang
- ORCID
- Venue
- Scientific Reports
- Published
- 2015-09-15
- Volume
- 5
- Issue
- 1
- Pages
- 14014-14014
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4642696
- OpenAlex
- W2218213969
- Cited by
- 90
- References
- 48
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 10 · 2021: 16 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 11 · 2016: 7 · 2015: 1
- FWCI
- 7.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2014CB548200, 10SYSYJC28400, 81201023)
- National Key Research and Development Program of China (2014CB548200, 2015CB553602)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- punicalagin, pomegranate extract, ellagitannins, obesity, high-fat diet, cardiac mitochondrial dysfunction, AMPK activation, mitochondrial biogenesis, oxidative stress, phase II enzymes, uncoupling proteins, mitochondrial dynamics, cardiomyocytes, myocardial energy metabolism, triglyceride accumulation, cholesterol accumulation
- MeSH terms
- Animals, Organelle Biogenesis, Mitochondria, Heart, Myocardium, Obesity, Phosphorylation, Signal Transduction, Oxidative Stress, Lythraceae, Myocytes, Cardiac, Hydrolyzable Tannins, Rats, AMP-Activated Protein Kinases, Diet, High-Fat
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