2. Academic Validation
  3. Ecliptasaponin A protects heart against acute ischemia-induced myocardial injury by inhibition of the HMGB1/TLR4/NF-κB pathway

Ecliptasaponin A protects heart against acute ischemia-induced myocardial injury by inhibition of the HMGB1/TLR4/NF-κB pathway

  • J Ethnopharmacol. 2024 Jul 22:335:118612. doi: 10.1016/j.jep.2024.118612.
Sumin Ge 1,  Sihua Wu 2,  Qin Yin 1,  Meng Tan 1,  Sichuan Wang 1,  Yonghao Yang 1,  Zixuan Chen 1,  Lei Xu 1,  Hui Zhang 3,  Chuang Meng 4,  Yufei Xia 5,  Naoki Asakawa 6,  Wenping Wei 7,  Kaizheng Gong 8,  Xin Pan 9
Affiliations

Affiliations

  • 1 Department of Cardiology, Department of Pediatrics, Central Laboratory, Cutting-edge Innovation Key Lab of Major CVD in Yangzhou, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu, China.
  • 2 Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu, Gunma, Japan; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
  • 3 School of Medicine, Yangzhou University, Yangzhou 225000, Jiangsu, China.
  • 4 Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225000, Jiangsu, China.
  • 5 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
  • 6 Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu, Gunma, Japan.
  • 7 Department of Cardiology, Department of Pediatrics, Central Laboratory, Cutting-edge Innovation Key Lab of Major CVD in Yangzhou, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu, China. Electronic address: weiwp_yzu@163.com.
  • 8 Department of Cardiology, Department of Pediatrics, Central Laboratory, Cutting-edge Innovation Key Lab of Major CVD in Yangzhou, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu, China. Electronic address: yungkzh@163.com.
  • 9 Department of Cardiology, Department of Pediatrics, Central Laboratory, Cutting-edge Innovation Key Lab of Major CVD in Yangzhou, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu, China. Electronic address: xinpanphd@163.com.
PMID: 39047883 DOI: 10.1016/j.jep.2024.118612
Abstract

Ethnopharmacological relevance: Eclipta prostrata (Linn.) is a traditional medicinal Chinese herb that displays multiple biological activities, such as encompassing immunomodulatory, anti-inflammatory, anti-tumor, liver-protective, antioxidant, and lipid-lowering effects. Ecliptasaponin A (ESA), a pentacyclic triterpenoid saponin isolated from Eclipta prostrata (Linn.), has been demonstrated to exert superior anti-inflammatory activity against many inflammatory disorders.

Aim of the study: Inflammation plays a critical role in acute myocardial infarction (AMI). This study aims to explore the treatment effects of ESA in AMI, as well as the underlying mechanism.

Methods: An AMI mouse model was established in mice via left anterior descending coronary artery (LAD) ligation. After surgery, ESA was injected at doses of 0.5, 1.25, and 2.5 mg/kg, respectively. Myocardial infarction size, cardiomyocyte Apoptosis and cardiac echocardiography were studied. The potential mechanism of action of ESA was investigated by RNA-seq, Western blot, surface plasmon resonance (SPR), molecular docking, and immunofluorescence staining.

Results: ESA treatment not only significantly reduced myocardial infarct size, decreased myocardial cell Apoptosis, and inhibited inflammatory cell infiltration, but also facilitated to improve cardiac function. RNA-seq and Western blot analysis proved that ESA treatment-induced differential expression genes mainly enriched in HMGB1/TLR4/NF-κB pathway. Consistently, ESA treatment resulted into the down-regulation of IL-1β, IL-6, and TNF-α levels after AMI. Furthermore, SPR and molecular docking results showed that ESA could bind directly to HMGB1, thereby impeding the activation of the downstream TLR4/NF-κB pathway. The immunofluorescence staining and Western blot results at the cellular level also demonstrated that ESA inhibited the activation of the HMGB1/TLR4/NF-κB pathway in H9C2 cells.

Conclusion: Our study was the first to demonstrate a cardiac protective role of ESA in AMI. Mechanism study indicated that the treatment effects of ESA are mainly attributed to its anti-inflammatory activity that was mediated by the HMGB1/TLR4/NF-κB pathway.

Keywords

Acute myocardial infarction; Eclipta prostrata (Linn.); Ecliptasaponin A; HMGB1/TLR4/NF-κB pathway; Inflammation.

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