Glycyrrhizic acid ameliorates myocardial ischemia-reperfusion injury in rats through inhibiting endoplasmic reticulum stress

Lai, Teng-Fang; Shen, Yong; Chen, Chengcai; Huang, Bo-Huei; Deng, Tongyuan; Zhao, Zhuang-Zhi; Zhang, Zhuohua; Huang, Zhaohe; Pan, Xingshou

doi:10.1016/j.ejphar.2021.174353

Cited by 13 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In one study, two doses of diammonium glycyrrhizinate, 15 mg/kg and 30 mg/kg, were found to have some effect in improving cerebral ischemia-reperfusion injury, suggesting a tendency of higher doses to have better improvement effect, but no statistical difference was mentioned. 36 Other glycyrrhizinate doses has been studied in organ ischemia-reperfusion injury at various doses, including 10 mg/kg 37 , 38 and 50 mg/kg 39 for myocardial ischemia-reperfusion, 50 mg/kg 40 for hepatic ischemia-reperfusion injury and 10 mg/kg 41 for spinal cord ischemia-reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

Effect of Diammonium Glycyrrhizinate in Improving Focal Cerebral Ischemia-Reperfusion Injury in Rats Through Multiple Mechanisms

Wang¹,

Zhang²,

Dong

et al. 2022

Dose-Response

View full text Add to dashboard Cite

Objective Acute ischemic stroke is a current major disabling and killer disease worldwide. We aimed to investigate the protective effect and mechanism of diammonium glycyrrhizinate in alleviating acute ischemic stroke. Methods Ninety male Sprague Dawley (SD) rats (weighing 250–300 g) were randomly allocated into three groups: sham operation group (sham group), diammonium glycyrrhizinate group (DG group) and model group (model group) each with 30 individuals. A rat model of focal CIR injury was established by reversible middle cerebral artery occlusion. Results Zea-Longa scores for the rats in the DG group and model group were 7-fold and 8-fold higher than those of the sham group 2 h post-surgery (2.90 ± 0.99 vs. 0.30 ± 0.53, P < .05; 2.80 ± 0.61 vs. 0.30 ± 0.53, P < .05, respectively). Three days after model establishment, the scores of DG group were 26.92% lower compared with those of the model group (1.90 ± 0.76 vs. 2.60 ± 0.62, P < .05). In addition, compared with the sham group, the number of Nissl bodies and Akt-positive cells in were 27.35% and 30.42% lower in the hippocampus of the DG group (Nissl bodies: 83.40 ± 7.01 vs. 115.60 ± 11.97, p < 0.05; Akt-positive cells: 94.70 ± 8.23 vs. 136.10 ± 10.37, P < .05) and 58.65% and 57.31% lower in the model group (Nissl bodies: 47.80 ± 4.91 vs. 115.60 ± 11.97, P < .05; Akt-positive cells: 58.10 ± 4.98 vs. 136.10 ± 10.37, P < 0.05), respectively. However, the number of Nissl bodies and Akt-positive cells in the hippocampus of DG group were 74.48% and 62.9% higher compared with the model group, respectively (Nissl bodies: 83.40 ± 7.01 vs. 47.80 ± 4, P < 0.05; Akt-positive cells: 94.70 ± 8.23 vs. 58.10 ± 4.98, P < .05). In addition, compared with the sham group, the number of caspase-3-positive cells, the expression level of p38 mitogen-activated protein kinase (MAPK) and the expression of matrix metallopeptidase 9 (MMP-9) were 2-fold, 34.38%, 64.78% higher in the DG group (caspase-3-positive cells: 78.70 ± 6.52 vs. 27.10 ±3.00, P < .05; p-38MAPK: 0.43 ± 0.15 vs. 0.32 ± 0.10, P < .05; MMP-9: 14.83 ± 1.18 vs. 9.00 ± 2.05, P < .05, respectively), and more than 3-fold, 1-fold and 1-fold higher in model group (caspase-3-positive cells: 121.10 ± 11.04 vs. 27.10 ± 3.00, P < .05; p-38MAPK: 0.70 ± 0.12 vs. 0.32 ± 0.10, P < .05; MMP-9: 19.00 ± 1.90 vs. 9.00 ± 2.05, P < .05), respectively. However, the number of caspase-3-positive cells and the expression levels of p-38MAPK and MMP-9 were 35.01%, 38.57% and 28.12% lower in DG group compared with the model group (caspase-3-positive cells: 78.70 ± 6.52 vs. 121.10 ± 11.04, P < .05; p-38MAPK: 0.43 ± 0.15 vs. 0.70 ± 0.12, P < .05; MMP-9: 14.83 ± 1.18 vs. 19.00 ± 1.90, P < .05). Conclusions Our study showed that diammonium glycyrrhizinate at 20 mg/kg/day had a protective effect on cerebral ischemia-reperfusion injury in rats by promoting formation of Nissl bodies and increasing protein expression of Akt while decreasing that of caspase-3, p38 MAPK and MMP-9, either directly or indirectly, by inhibiting apoptosis and reducing neuroinflammation. All these mechanisms resulted in improved overall neurological function.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Diammonium Glycyrrhizinate in Improving Focal Cerebral Ischemia-Reperfusion Injury in Rats Through Multiple Mechanisms

Wang¹,

Zhang²,

Dong

et al. 2022

Dose-Response

View full text Add to dashboard Cite

show abstract

“…Twenty male rats went through left anterior descending (LAD) coronary artery ligation and reperfusion to induce myocardial ischemia/ reperfusion (I/R) model. 29 Briefly, the rats were anaesthetized with sodium pentobarbital (50 mg/kg i.p.) prior to surgery.…”

Section: Animal and Exosome Treatmentmentioning

confidence: 99%

Exosomal miR-455-3p from BMMSCs prevents cardiac ischemia-reperfusion injury

Wang

Shen

2022

Hum Exp Toxicol

View full text Add to dashboard Cite

Objective Bone marrow mesenchymal stem cells (BMMSCs) exert protective effects against myocardial infarction (MI). Here, we focused on the function and mechanism of miR-455-3p from BMMSCs-derived exosomes (BMMSCs-Exo) in myocardial infarction. Materials and methods BMMSCs were isolated from rat bone marrow, and the exosomes from the culture medium of BMMSCs were separated, and administered to H9C2 cells under hypoxia-reperfusion (H/R) stimulation. MTT and TUNEL staining analyzed cell viability and apoptosis, respectively. RT-qPCR determined miR-455-3p expression. Apoptosis-related proteins, autophagy-associated proteins, and the MEKK1-MKK4-JNK signaling pathway were detected. The interaction between miR-455-3p and MEKK1 was confirmed through dual luciferase activity and RIP assay. An in vivo ischemia reperfusion (I/R) model was established in rats. 2, 3, 5 triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, Masson staining, and TUNEL staining evaluated the infarct volume and histopathological changes. Results miR-455-3p′s expression was down-regulated in BMMSCs-derived exosomes, I/R myocardial tissues, and H/R myocardial cells. miR-455-3p enriched by BMMSC exosomes reduced H/R-mediated cardiomyocyte damage and death-related autophagy. miR-455-3p upregulation suppressed MEKK1-MKK4-JNK. MEKK1 overexpression notably mitigated cell apoptosis, cramped cell viability, suppressed autophagy expansion, and attenuated Exo-miR-455-3p′s protection on H/R myocardial cells. In-vivo trials reflected that BMMSC exosomes enriched with miR-455-3p repressed ischemia reperfusion-induced myocardial damage and myocardial cell function. Conclusion miR-455-3p, shuttled by exosomes from MSCs, targets the MEKK1-MKK4-JNK signaling pathway to guard against myocardial ischemia-reperfusion damage.

show abstract

“…Apoptosis is a type of programmed cell death, characterized by cell shrinkage, chromatin condensation, and nuclear shrinkage ( Hotchkiss et al, 2009 ). Apoptosis pathways include the death receptor apoptosis pathway, mitochondria apoptosis pathway, endoplasmic reticulum (ER) pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway ( Hotchkiss et al, 2009 ; Lai et al, 2021 ; Zhu and Zhou, 2021 ). Death receptors are activated by their ligands, namely, FasL, TNF-α, and TRAIL ( Zhang et al, 2019a ).…”

Section: Myocardial Cell Apoptosis In Myocardial Ischemia/reperfusion...mentioning

confidence: 99%

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury

Chen

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Ischemic heart disease has a high mortality, and the recommended therapy is reperfusion. Nevertheless, the restoration of blood flow to ischemic tissue leads to further damage, namely, myocardial ischemia/reperfusion injury (MIRI). Apoptosis is an essential pathogenic factor in MIRI, and ginsenosides are effective in inhibiting apoptosis and alleviating MIRI. Here, we reviewed published studies on the anti-apoptotic effects of ginsenosides and their mechanisms of action in improving MIRI. Each ginsenoside can regulate multiple pathways to protect the myocardium. Overall, the involved apoptotic pathways include the death receptor signaling pathway, mitochondria signaling pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway, and MAPK signaling pathway. Ginsenosides, with diverse chemical structures, regulate different apoptotic pathways to relieve MIRI. Summarizing the effects and mechanisms of ginsenosides contributes to further mechanism research studies and structure–function relationship research studies, which can help the development of new drugs. Therefore, we expect that this review will highlight the importance of ginsenosides in improving MIRI via anti-apoptosis and provide references and suggestions for further research in this field.

show abstract

Glycyrrhizic acid ameliorates myocardial ischemia-reperfusion injury in rats through inhibiting endoplasmic reticulum stress

Cited by 13 publications

References 19 publications

Effect of Diammonium Glycyrrhizinate in Improving Focal Cerebral Ischemia-Reperfusion Injury in Rats Through Multiple Mechanisms

Effect of Diammonium Glycyrrhizinate in Improving Focal Cerebral Ischemia-Reperfusion Injury in Rats Through Multiple Mechanisms

Exosomal miR-455-3p from BMMSCs prevents cardiac ischemia-reperfusion injury

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury

Contact Info

Product

Resources

About