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The roles of the mitophagy inducer Danqi pill in heart failure: A new therapeutic target to preserve energy metabolism.
Wang, Xiaoping; Jiang, Yanyan; Zhang, Yawen; Sun, Qianbin; Ling, Guanjing; Jiang, Jinchi; Li, Weili; Tian, Xue; Jiang, Qianqian; Lu, Linghui; Wang, Yong.
Affiliation
  • Wang X; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Jiang Y; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Zhang Y; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Sun Q; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Ling G; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Jiang J; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Li W; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Tian X; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Jiang Q; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
  • Lu L; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: lu-linghui@hotmail.com.
  • Wang Y; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing 100029, China; Key Laboratory of Beijing Universit
Phytomedicine ; 99: 154009, 2022 May.
Article in En | MEDLINE | ID: mdl-35217438
BACKGROUND: Mitophagy can regulate mitochondrial homeostasis, preserve energy metabolism and cardiomyocytes survival effectively to restrain the development of heart failure (HF). Danqi Pill (DQP), composed of the dry roots of Salvia miltiorrhiza Bunge and Panax notoginseng, is included in the 2015 national pharmacopeia and effective in the clinical treatment of coronary heart diseases. Our previous studies have approved that DQP exerted remarkable cardioprotective effects on HF. However, the effect and mechanism of DQP on mitophagy have not been proved yet. HYPOTHESIS/PURPOSE: We aim to explore whether DQP regulates mitophagy to protect against HF and to elucidate the in-depth mechanism. STUDY DESIGN: The HF rat model for evaluating DQP's efficacy was established with left anterior descending coronary artery ligation. The oxygen-glucose deprivation-reperfusion-induced cardiomyocyte model was conducted to clarify the potential mechanism of DQP. METHODS: The mitochondria-targeted fluorescent protein Keima (mt-Keima) was applied for detecting mitophagy flux. Co-immunofluorescence and co-immunoprecipitation were performed to detect protein co-localization. Flow cytometry for JC-1 and Annexin-FITC/PI staining was utilized for assessing mitochondrial activity and function. RESULTS: In vivo, medium dose of DQP (1.5 g/kg) notably improved cardiac function and inhibited cardiac apoptosis in HF rats. Co-immunofluorescent staining of LC3B and TOM20 showed that DQP restored mitophagy. Further co-immunoprecipitation demonstrated that DQP increased the co-localization of FUNDC1 with either ULK1 or PGAM5. In vitro, DQP markedly protected mitochondrial membrane potential damage, reduced cardiomyocytes apoptosis, decreased the level of mitochondrial ROS, and increased the ATP level. Parallel with the in vitro results, DQP increased the interaction of FUNDC1 and LC3B, while knockdown of FUNDC1 diminished the interaction. Besides, Mt-Keima signaling detection further confirmed that DQP significantly promoted mitophagy. Intriguingly, knockdown of ULK1 or PGAM5 separately weakened rather than eliminated these effects of DQP on FUNDC1-mediated mitophagy, mitochondrial homeostasis and energy metabolism. CONCLUSION: Our results demonstrated that DQP protected against HF by improving FUNDC1-mediated mitophagy to perverse energy metabolism through the coordinated regulation of ULK1 and PGAM5.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Phytomedicine Journal subject: TERAPIAS COMPLEMENTARES Year: 2022 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Phytomedicine Journal subject: TERAPIAS COMPLEMENTARES Year: 2022 Document type: Article Affiliation country: Country of publication: