ReferenceID 6085
Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway
Acta Pharmacol Sin
Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phyt
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- Reference Id
- 6085
- Evidence Id
- 22675
- Core Evidence Id
- 22675
- Source Reference Id
- 5431
- Herb2 Reference Id
- HBREF006228
- Subject Paper Key
- HBIN041253_32504066
- Pubmed Id
- 32504066
- Doi
- 10.1038/s41401-020-0401-y
- Paper Title
- Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway
- Paper Abstract
- Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg kg-1 d-1, ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARalpha/PPARgamma coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor alpha, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 muM), which was attenuated by co-treatemnt with puerarin (100 muM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARalpha antagonist GW6471 (10 muM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARalpha/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.
- Journal
- Acta Pharmacol Sin
- Publish Year
- 2021
- Experiment Subject
- rat; patient; women
- Experiment Type
- Animal Experiment
- Phenotype Related
- Cardiac Hypertrophy; Heart Failure; Cardiovascular Disease; Cardiac Dysfunction; Abdominal Aortic Constriction; Mitochondrial Dysfunction; Bilateral Oophorectomy; Estrogen Deficiency
- Paper Title Cn
- Paper Title En
- Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway
- Bilingual Status
- semi_complete