Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism
Introduction: Valerenic acid (VA) is a unique and biologically active component in Valeriana officinalis L., which has been reported to have a regulatory effect on the cardiovascular system. However, its therapeutic effects on pathological myocardial hypertrophy (PMH) and the underlying mechanisms a...
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Elsevier
2025-02-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000705 |
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| author | Tiantian Liu Xu Chen Qianbin Sun Junjun Li Qiyan Wang Peng Wei Wei Wang Chun Li Yong Wang |
| author_facet | Tiantian Liu Xu Chen Qianbin Sun Junjun Li Qiyan Wang Peng Wei Wei Wang Chun Li Yong Wang |
| author_sort | Tiantian Liu |
| collection | DOAJ |
| description | Introduction: Valerenic acid (VA) is a unique and biologically active component in Valeriana officinalis L., which has been reported to have a regulatory effect on the cardiovascular system. However, its therapeutic effects on pathological myocardial hypertrophy (PMH) and the underlying mechanisms are undefined. Objectives: Our study aims to elucidate how VA improves PMH, and preliminarily discuss its mechanism. Methods: The efficacy of VA on PMH was confirmed by in vivo and in vitro experiments and the underlying mechanism was investigated by molecular dynamics (MD) simulations and specific siRNA interference. Results: VA enhanced cardiomyocyte fatty acid oxidation (FAO), inhibited hyper-activated glycolysis, and improved the unbalanced pyruvate-lactate axis. VA could significantly improve impaired mitochondrial function and reduce the triglyceride (TG) in the hypertrophic myocardium while reducing the lactate (LD) content. Molecular mechanistic studies showed that VA up-regulated the expression of peroxisome proliferator-activated receptor-α (PPARα) and downstream FAO-related genes including CD36, CPT1A, EHHADH, and MCAD. VA reduced the expression of ENO1 and PDK4, the key enzymes in glycolysis. Meanwhile, VA improved the pyruvate-lactate axis and promoted the aerobic oxidation of pyruvate by inhibiting LDAH and MCT4. MD simulations confirmed that VA can bind with the F273 site of PPARα, which proposes VA as a potential activator of the PPARα. Conclusion: Our results demonstrated that VA might be a potent activator for the PPARα-mediated pathway. VA directly targets the PPARα and subsequently promotes energy metabolism to attenuate PMH, which can be applied as a potentially effective drug for the treatment of HF. |
| format | Article |
| id | doaj-art-d3bdc42ecc614736bc97917d304d424c |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-d3bdc42ecc614736bc97917d304d424c2025-01-18T05:04:17ZengElsevierJournal of Advanced Research2090-12322025-02-0168241256Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolismTiantian Liu0Xu Chen1Qianbin Sun2Junjun Li3Qiyan Wang4Peng Wei5Wei Wang6Chun Li7Yong Wang8College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaCollege of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaCollege of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, ChinaBeijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing 100029, ChinaCollege of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing 100029, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangdong 510006, China.; Corresponding authors at: Beijing University of Chinese Medicine, No. 11, North 3rd Ring East Road, Chaoyang District, Beijing City 100029, China.Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing 100029, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangdong 510006, China.; Corresponding authors at: Beijing University of Chinese Medicine, No. 11, North 3rd Ring East Road, Chaoyang District, Beijing City 100029, China.College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China; Yunnan University of Chinese Medicine, Yunnan 650500, China; Corresponding authors at: Beijing University of Chinese Medicine, No. 11, North 3rd Ring East Road, Chaoyang District, Beijing City 100029, China.Introduction: Valerenic acid (VA) is a unique and biologically active component in Valeriana officinalis L., which has been reported to have a regulatory effect on the cardiovascular system. However, its therapeutic effects on pathological myocardial hypertrophy (PMH) and the underlying mechanisms are undefined. Objectives: Our study aims to elucidate how VA improves PMH, and preliminarily discuss its mechanism. Methods: The efficacy of VA on PMH was confirmed by in vivo and in vitro experiments and the underlying mechanism was investigated by molecular dynamics (MD) simulations and specific siRNA interference. Results: VA enhanced cardiomyocyte fatty acid oxidation (FAO), inhibited hyper-activated glycolysis, and improved the unbalanced pyruvate-lactate axis. VA could significantly improve impaired mitochondrial function and reduce the triglyceride (TG) in the hypertrophic myocardium while reducing the lactate (LD) content. Molecular mechanistic studies showed that VA up-regulated the expression of peroxisome proliferator-activated receptor-α (PPARα) and downstream FAO-related genes including CD36, CPT1A, EHHADH, and MCAD. VA reduced the expression of ENO1 and PDK4, the key enzymes in glycolysis. Meanwhile, VA improved the pyruvate-lactate axis and promoted the aerobic oxidation of pyruvate by inhibiting LDAH and MCT4. MD simulations confirmed that VA can bind with the F273 site of PPARα, which proposes VA as a potential activator of the PPARα. Conclusion: Our results demonstrated that VA might be a potent activator for the PPARα-mediated pathway. VA directly targets the PPARα and subsequently promotes energy metabolism to attenuate PMH, which can be applied as a potentially effective drug for the treatment of HF.http://www.sciencedirect.com/science/article/pii/S2090123224000705Valerenic acidPathological myocardial hypertrophyFatty acid metabolismPyruvate-lactate axisPPARα pathway |
| spellingShingle | Tiantian Liu Xu Chen Qianbin Sun Junjun Li Qiyan Wang Peng Wei Wei Wang Chun Li Yong Wang Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism Journal of Advanced Research Valerenic acid Pathological myocardial hypertrophy Fatty acid metabolism Pyruvate-lactate axis PPARα pathway |
| title | Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism |
| title_full | Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism |
| title_fullStr | Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism |
| title_full_unstemmed | Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism |
| title_short | Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism |
| title_sort | valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism |
| topic | Valerenic acid Pathological myocardial hypertrophy Fatty acid metabolism Pyruvate-lactate axis PPARα pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000705 |
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