2. Academic Validation
  3. Ginsenoside Rb1 promotes the activation of PPARα pathway via inhibiting FADD to ameliorate heart failure

Ginsenoside Rb1 promotes the activation of PPARα pathway via inhibiting FADD to ameliorate heart failure

  • Eur J Pharmacol. 2023 Mar 30;947:175676. doi: 10.1016/j.ejphar.2023.175676.
Chuting Li 1,  Xuting Zhang 1,  Jie Li 2,  Liyin Liang 1,  Jingran Zeng 1,  Min Wen 1,  Linjie Pan 1,  Dongxin Lv 1,  Min Liu 3,  Yuanyuan Cheng 4,  Heqing Huang 5
Affiliations

Affiliations

  • 1 Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
  • 2 Medical Research Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
  • 3 Guangzhou University of Traditional Chinese Medicine First Affiliated Hospital, Guangzhou, 510405, China. Electronic address: [email protected].
  • 4 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. Electronic address: [email protected].
  • 5 Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address: [email protected].
PMID: 37001580 DOI: 10.1016/j.ejphar.2023.175676
Abstract

Purpose: Ginsenoside Rb1 (GRb1), a dammarane-type triterpene saponin compound mainly distributed in ginseng (Panax ginseng), has been demonstrated to ameliorate cardiovascular diseases. However, it remains unclear whether GRb1 alleviates heart failure (HF) by maintaining cardiac energy metabolism balance. Therefore, this work aimed to investigate the cardiac benefits of GRb1 against cardiac energy deficit and explore its mechanism of action.

Methods and results: Isoproterenol (ISO) induced HF Sprague-Dawley rats were administrated with GRb1 or fenofibrate for 6 weeks. ISO-induced primary neonatal rat cardiomyocytes (NRCMs) were used as the in vitro model. In vivo, GRb1 significantly improved the structural and metabolic disorder, as demonstrated by the restoration of cardiac function, inhibition of cardiac hypertrophy and fibrosis, and increased adenosine triphosphate (ATP) generation. In vitro, GRb1 effectively protected mitochondrial function and scavenged excessive Reactive Oxygen Species. Moreover, in ISO-induced NRCMs, GRb1 significantly inhibited the abnormal upregulation of Fas-associated death domain (FADD), promoted transcriptional activation of peroxisome proliferator-activated receptor-alpha (PPARα), improved the aberrant expression of cardiac energy metabolism-related enzymes and cardiac fatty acid oxidation, and subsequently increased the synthesis of ATP. Noticeably, GRb1 could inhibit the increased binding between FADD and PPARα, which contributed to the activation of PPARα. Furthermore, GRb1 strengthened the thermal stabilization of FADD and might bind to FADD directly.

Conclusions: Collectively, it's part of the in-depth mechanism of GRb1's cardio-protection that GRb1 could directly bind to FADD and counteract its negative role in the transcription of PPARα thus ameliorating cardiac energy derangement and HF.

Keywords

Cardiac energy metabolism; FADD; Fatty acid oxidation; Ginsenoside Rb1; Heart failure; PPARα.

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