Isoliquiritigenin alleviates LPS/ D-GalN-induced acute liver failure by activating the PGC-1α/ Nrf2 pathway to reduce oxidative stress and inflammatory response

Wang, Lu; Wang, Xiaohui; Kong, Lina; Wang, Shuyuan; Huang, Kai; Wu, Jingjing; Wang, Changyuan; Sun, Huijun; Liu, Kexin; Meng, Qiang

doi:10.1016/j.intimp.2021.108159

Cited by 27 publications

(17 citation statements)

References 35 publications

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“… 25 The main function of ISL is to counteract oxidative stress and inflammation. 24 , 26 Since oxidative stress and inflammation play essential roles in the pathophysiology of the acute phase of AMI, inhibiting them might be beneficial; 5 , 27 , 28 thus, we tested the effect of ISL in the treatment of mouse with AMI. We found that the dose of 100 mg/kg/day of ISL could reduce the myocardial infarction size and restore cardiac function.…”

Section: Discussionmentioning

confidence: 99%

“…Nrf2 is a vital transcription factor that regulates the levels of antioxidant enzymes in cells. 16 , 24 , 26 In normal conditions, cytoplasmic Nrf2 content is strictly regulated by Keap1 (redox-sensitive E3 ubiquitin ligase substrate adapter). 29 Two Keap1 molecules bind to one Nrf2 to regulate the continuous ubiquitination and degradation.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, several studies have reported that ISL could also inhibit inflammatory responses by inhibiting the activation of NLRP3 inflammasome in different models. 26 , 46 , 47 Therefore, Nrf2 and NF-κB pathway may be one of the main inflammatory regulators in ISL treatment for AMI in the early acute stage. We could not exclude cross-talking with other pathways, which could be effective to control inflammation response in different conditions.…”

Section: Discussionmentioning

confidence: 99%

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Isoliquiritigenin Ameliorates Ischemia-Induced Myocardial Injury via Modulating the Nrf2/HO-1 Pathway in Mice

Yao¹,

Shen²,

Wang³

et al. 2022

DDDT

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Background Oxidative stress and inflammatory reaction play critical roles in acute myocardial infarction (AMI). Isoliquiritigenin (ISL), a flavonoid monomer extracted from licorice, has been found to have antioxidant and anti-inflammatory effects in cancer studies. Here, we tested the effect and underlying mechanisms of ISL on ischemia-induced myocardial injury in a mouse AMI model. Methods Adult C57BL/6 mice were pre-treated by intraperitoneal injection of ISL and/or a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 for 3 days, respectively. Then, the AMI model was established by ligating the anterior descending branch of the left coronary artery. Myocardial oxidative stress status, inflammatory response, cardiac function and infarction size were assessed after 7th day of surgery. Results Compared with sham group, the reactive oxygen species (ROS) and malondialdehyde (MDA) level in AMI group were significantly increased. However, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level were dramatically decreased. ISL treatment significantly reduced the myocardial infarction area, improved cardiac function, inhibited the production of ROS and MDA and reduced the consumption of SOD and GSH-Px. Interestingly, ISL could significantly increase nuclear Nrf2 and cytosolic heme oxygenase 1 (HO-1) level in the infarcted myocardium and reduce the oxidative stress after AMI. Also, ISL treatment dramatically inhibited the activation of myocardial NF-κB pathway and reduced the expression of pro-inflammatory factors in the AMI group. However, the administration of ML385 not only suppressed the Nrf2/HO-1 activation, the anti-oxidant and anti-inflammatory effects induced by ISL, but also attenuated the beneficial role of ISL on reducing infarct size and improving cardiac function in the mouse with AMI. Conclusion The results suggested that activation of Nrf2/HO-1 pathway has an essential role in ISL-induced cardiac protection by alleviating myocardial oxidative stress and inflammation response in mice with AMI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Isoliquiritigenin Ameliorates Ischemia-Induced Myocardial Injury via Modulating the Nrf2/HO-1 Pathway in Mice

Yao¹,

Shen²,

Wang³

et al. 2022

DDDT

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“… 60 Increased accumulation and infiltration of inflammatory cells may induce apoptosis. 61 p-CA pre-treatment during this study clearly elaborated the protective effects against LPS/D-GalN induced inflammatory response while improving hepatic necrosis and increasing the level of anti-oxidants. 62 p-CA had alleviated the overproduction of inflammatory mediators eg TNF-α, IL-6 and IL-1β in liver tissue, which suggested its anti-inflammation activity in liver injury.…”

Section: Discussionmentioning

confidence: 70%

Protective Effects of p-CA Against Acute Liver Damage Induced by LPS/D-GalN in Wistar Albino Rats

Mehdi¹,

Ahmad²,

Lodhi³

et al. 2022

DDDT

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Liver regulates metabolism of biomolecules and injury of liver causes distortion of metabolic functions. This injury may be oxidative or inflammatory induced by numerous factors including alcohol, pathogens and xenobiotics. This scientific study was planned to investigate the anti-inflammatory and anti-oxidant potential of p-coumaric acid (p-CA) on Lipopolysaccharide/ D-Galactosamine (LPS/D-GalN) induced liver injury. Methods: DPPH analysis, reducing power assay and HPLC analysis were performed during in-vitro studies of p-CA. Similarly, in-vivo experiments were performed using Wistar Albino rats. Normal control and intoxicated group received (5mL/kg normal saline p.o), standard treatment groups received ascorbic acid (100mg/kg p.o) and silymarin (25mg/kg p.o), while p-CA treatment groups received (100mg/kg p.o) for 28-days. After completion of 28-days, LPS/D-GalN injection (300 mg D-GalN/kg and 10 µg LPS/kg i.p.) was given at 6th, 12th and 24-hours to all groups except normal control group. Animals were sacrificed; serum and liver samples were harvested and subjected to biochemical and histological examinations, respectively. Results: The results revealed that p-CA possess strong antioxidant activity. Increased levels of leukocyte infiltration (TLC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), lipid panel (eg TG, TC, LDL-C, VLDL-C), whereas decreased HDL-C levels noticed in LPS/D-GalN groups as compared to normal control groups. Pro-Inflammatory markers (eg TNF-α, IL-6, IL-1β) and lipid peroxidation marker, eg malondialdehyde (MDA) increased while superoxide dismutase (SOD) and reduced glutathione (GSH) levels were decreased significantly in groups treated with LPS/D-GalN. ANOVA with Bonferroni post hoc analysis was used for statistical analysis of. H&E staining was done to assess architectural abnormalities among liver cells. Conclusion:In conclusion, p-CA could ameliorate LPS/D-GalN induced hepatic injury via regulation of immune responses, liver function enzymes, lipid profile, oxidative stress and pro-inflammatory markers.

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“…At the same time, because of its high permeability through the BBB, it has a more potent effect on the central nervous system, which provides it with better clinical application potential. In addition, in the drug treatment of acute liver failure, studies have proved that isoliquiritigenin can improve the ability of antioxidant stress and reduce both inflammatory reaction and apoptosis by activating PGC1-α/Nrf2 signaling pathway, which provides the possibility of treating acute liver failure [ 102 ]. Therefore, isoliquiritigenin and puerarin have the ability to regulate PGC1-α/Nrf2 signaling pathway, while isoliquiritigenin has the potential to regulate Nrf2 through various Keap1-independent signaling pathways.…”

Section: Nrf2 Activator In the Treatment Of Asahmentioning

confidence: 99%

Pharmacological Modulations of Nrf2 and Therapeutic Implications in Aneurysmal Subarachnoid Hemorrhage

Qia

Zhang

2023

Molecules

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An aneurysmal subarachnoid hemorrhage (aSAH) is a subtype of stroke with high morbidity and mortality. The main causes of a poor prognosis include early brain injury (EBI) and delayed vasospasm, both of which play a significant role in the pathophysiological process. As an important mechanism of EBI and delayed vasospasm, oxidative stress plays an important role in the pathogenesis of aSAH by producing reactive oxygen species (ROS) through the mitochondria, hemoglobin, or enzymatic pathways in the early stages of aSAH. As a result, antioxidant therapy, which primarily targets the Nrf2-related pathway, can be employed as a potential strategy for treating aSAH. In the early stages of aSAH development, increasing the expression of antioxidant enzymes and detoxifying enzymes can relieve oxidative stress, reduce brain damage, and improve prognosis. Herein, the regulatory mechanisms of Nrf2 and related pharmacological compounds are reviewed, and Nrf2-targeted drugs are proposed as potential treatments for aSAH.

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Isoliquiritigenin alleviates LPS/ D-GalN-induced acute liver failure by activating the PGC-1α/ Nrf2 pathway to reduce oxidative stress and inflammatory response

Cited by 27 publications

References 35 publications

Isoliquiritigenin Ameliorates Ischemia-Induced Myocardial Injury via Modulating the Nrf2/HO-1 Pathway in Mice

Isoliquiritigenin Ameliorates Ischemia-Induced Myocardial Injury via Modulating the Nrf2/HO-1 Pathway in Mice

Protective Effects of p-CA Against Acute Liver Damage Induced by LPS/D-GalN in Wistar Albino Rats

Pharmacological Modulations of Nrf2 and Therapeutic Implications in Aneurysmal Subarachnoid Hemorrhage

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