Abstract | BACKGROUND: METHODS AND RESULTS: The anti- hypertrophy effect of TMYX was validated in isoproterenol-induced cardiac hypertrophy model in C57BL/6 mice. After TMYX treatment for 2 weeks, the heart ejection fraction and fractional shortening of the mice model was increased by approximately 20% and 15%, respectively, (p < 0.05). Besides, TMYX dose-dependently reduced the cross section area of cardiomyocytes in the angiotensin-II induced hypertrophy H9c2 model (p < 0.01). Combining high content screening and liquid chromatography mass spectrometry, four compounds with anti- cardiac hypertrophy effects were identified from TMYX, which includes emodin, licoisoflavone A, licoricone and glyasperin A. Licoisoflavone A is one of the compounds with most significant protective effect and we continued to investigate the mechanism. Primary cultures of neonatal rat cardiomyocytes were treated with a hypertrophic agonist phenylephrine (PE) in the presence or absence of licoisoflavone A. After 48 h of treatment, cells were harvested and mitochondrial acetylation was analyzed by western blotting and Image analysis. Interestingly, the results suggested that the anti-hypertrophic effects of licoisoflavone A depend on the activation of the deacetylase Sirt3 (p < 0.01). Finally, we showed that licoisoflavone A-treatment was able to decrease relative ANF and BNP levels in the hypertrophic cardiac cells (p < 0.01), but not in cells co-treated with Sirt3 inhibitors (3-TYP) (p > 0.05). CONCLUSION:
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Authors | Rui Guo, Ningning Liu, Hao Liu, Junhua Zhang, Han Zhang, Yingchao Wang, Mirko Baruscotti, Lu Zhao, Yi Wang |
Journal | Phytomedicine : international journal of phytotherapy and phytopharmacology
(Phytomedicine)
Vol. 68
Pg. 153171
(Mar 2020)
ISSN: 1618-095X [Electronic] Germany |
PMID | 32018211
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Elsevier GmbH. All rights reserved. |
Chemical References |
- Drugs, Chinese Herbal
- Isoflavones
- Sirt3 protein, mouse
- tongmaiyangxin
- Angiotensin II
- Phenylephrine
- licoisoflavone A
- Sirtuin 3
- Isoproterenol
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Topics |
- Acetylation
- Angiotensin II
(adverse effects)
- Animals
- Cardiomegaly
(chemically induced, drug therapy)
- Cells, Cultured
- Disease Models, Animal
- Drug Evaluation, Preclinical
- Drugs, Chinese Herbal
(chemistry, pharmacology)
- Isoflavones
(pharmacology)
- Isoproterenol
(adverse effects)
- Male
- Mice, Inbred C57BL
- Mitochondria, Heart
(drug effects, metabolism)
- Myocytes, Cardiac
(drug effects, metabolism, pathology)
- Phenylephrine
(adverse effects)
- Rats
- Sirtuin 3
(metabolism)
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