2. Academic Validation
  3. Glycyrrhizic acid alleviated MI/R-induced injuries by inhibiting Hippo/YAP signaling pathways

Glycyrrhizic acid alleviated MI/R-induced injuries by inhibiting Hippo/YAP signaling pathways

  • Cell Signal. 2024 Jan 5:111036. doi: 10.1016/j.cellsig.2024.111036.
Xian Cheng 1,  Yanwu Liu 2,  Bingcai Qi 2,  Yuchao Wang 3,  Yue Zheng 3,  Xiaoyu Liang 4,  Yun Chang 4,  Meng Ning 4,  Wenqing Gao 5,  Tong Li 6
Affiliations

Affiliations

  • 1 The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China; Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China. Electronic address: cx0901@tmu.edu.cn.
  • 2 The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China; Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China.
  • 3 Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; School of Medicine, Nankai University, Tianjin 300071, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China.
  • 4 Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China.
  • 5 Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; School of Medicine, Nankai University, Tianjin 300071, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China. Electronic address: gaowenqing0906@126.com.
  • 6 The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China; Department of Heart Center, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; School of Medicine, Nankai University, Tianjin 300071, China; Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China; Tianjin ECMO Treatment and Training Base, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin, China. Electronic address: litong3zx@sina.com.
PMID: 38185229 DOI: 10.1016/j.cellsig.2024.111036
Abstract

Background: Previous research has demonstrated that glycyrrhizic acid (GA) exhibits antioxidant, anti-inflammatory, and antiapoptotic characteristics. Using myocardial ischemia/reperfusion injury as a case study, this study aims to clarify the functional significance of GA and to elucidate the mechanisms involved.

Materials and methods: In this study, an MI/R injury model was established both in vivo and in vitro to investigate the impact of GA on MI/R injury. The viability of H9c2 cells was evaluated using the Cell Counting Kit-8. Myocardial damage was assessed through the measurement of creatine kinase myocardial band (CK-MB) levels and Lactate Dehydrogenase (LDH), HE staining, and MASSON staining. Inflammatory cytokine levels (IL-6, IL-1β, IL-10, and TNF-α) were measured to determine the presence of inflammation. Cellular oxidative stress was evaluated by measuring ROS and MMP levels, while cardiac function was assessed using cardiac color Doppler ultrasound. Immunofluorescence staining to determine the nuclear translocation of YAP, TUNEL to determine Apoptosis, and western blotting to determine gene expression.

Results: GA treatment effectively alleviated myocardial injury induced by MI/R, as evidenced by reduced levels of inflammatory cytokines (IL-1β, IL-6, IL-10, and TNF-α) and cardiac biomarkers (CK-MB, LDH) in MI/R rats. Moreover, There was a significant increase in cell viability in vitro after GA treatment and inhibited Reactive Oxygen Species (ROS) during oxidative stress, while also increasing mitochondrial membrane potential (MMP) in vitro. The Western blot findings indicate that GA treatment effectively suppressed Apoptosis in both in vivo and in vitro settings. Additionally, GA demonstrated inhibitory effects on the activation of the Hippo/YAP signaling pathway triggered by MI/R and facilitated YAP nuclear translocation both in vitro and in vivo. It has been found, however, in vitro, that silencing the YAP gene negates GA's protective effect against hypoxia/reoxygenation-induced myocardial injury.

Conclusion: This study suggests that GA regulates YAP nuclear translocation by inhibiting the Hippo/YAP signaling pathway, which protects ists against MI/R injury. This finding may present a novel therapeutic approach for the treatment of MI/R.

Keywords

Apoptosis; Glycyrrhizic acid; Hippo/YAP signaling pathway; Myocardial ischemia-reperfusion injury; Oxidative stress.

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