Isoliquiritigenin attenuates inflammation and modulates Nrf2/caspase-3 signalling in STZ-induced aortic injury

Alzahrani, Sharifa; Said, Eman; Ajwah, Sadeem M.; Alsharif, Sumayyah Yasser; El-Bayoumi, Khaled S; Zaitone, Sawsan A.; Qushawy, Mona; Elsherbiny, Nehal M.

doi:10.1093/jpp/rgaa056

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…Previous studies have confirmed that Nrf2 is an important target against oxidative stress. 16 , 23 , 24 Given that Nrf2 mainly enters the nucleus to exert its biological functions, 16 we detected Nrf2 level in the nucleus after AMI. Western blot analysis showed that the level of Nrf2 in the nucleus and its downstream target HO-1 were increased due to oxidative stress ( Figure 5A and B ).…”

Section: Resultsmentioning

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: Resultsmentioning

confidence: 99%

“…ISL has been extensively studied in multiple pathological processes, such as diabetic cardiomyopathy 23 and intracerebral hemorrhage. 25 The main function of ISL is to counteract oxidative stress and inflammation.…”

Section: Discussionmentioning

confidence: 99%

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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“…Caspase-3 and Caspase-9 are involved in signal transduction of the death receptor apoptosis pathway and mitochondrial apoptosis pathway, respectively [ 20 ]. Finally, caspase-3 is activated and apoptosis is performed through cascade activation of multiple downstream caspase molecules [ 21 , 22 ]. Paeoniflorin is the active ingredient of Paeonia lactiflora, which can protect cells from inflammation and oxidation [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin Protects H9c2 Cardiomyocytes against Hypoxia/Reoxygenation Induced Injury via Regulating the AMPK/Nrf2 Signaling Pathway

Sun

Tan

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Myocardial ischemia/reperfusion (MIR) injury contributes to the exacerbation of heart disease by causing cardiac arrhythmias, myocardial infarction, and even sudden death. Studies have found that paeoniflorin (PF) has a protective effect on coronary artery disease (CAD). However, the mechanism of PF in MIR has not been fully investigated. The purpose of this study was to investigate the functional role of PF in H9c2 cells subjected to hypoxia/reoxygenation (H/R). Here, PF treatment enhanced cell viability in H/R-stimulated H9c2 cells. In H9c2 cells, PF treatment reduced the formation of reactive oxygen species (ROS) induced by H/R. In H/R-stimulated H9c2 cells, PF also increased the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. Furthermore, PF protected H9c2 cells against H/R-induced apoptosis, as demonstrated by increased Bcl-2 expression, decreased Bax expression, and decreased caspase-3 activity. Furthermore, PF increased the levels of p-AMPK and nuclear Nrf2 expression in response to H/R stimulation. AMPK inhibition, on the other hand, abolished the PF-mediated increase in Nrf2 signaling and the cardiac-protective effect in H9c2 cells exposed to H/R. These data suggest that PF protected H9c2 cells against H/R-induced oxidative stress and apoptosis through modulating the AMPK/Nrf2 signaling pathway. Our findings support the therapeutic potential of PF in myocardial I/R damage.

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“…The antidiabetic and antidepressant profile of MSE is obviously supported by its chemical constituents. For instance, isoliquiritigenin attenuated DM-induced renal and aortic injury, and displayed significant neuroprotective and antidepressant effects via its effects of oxidative stress and inflammation [ 45 , 46 , 47 ]. Silvestro et al reported that quercetin displayed antidepressant-like actions due to its antioxidant, anti-inflammatory and neuroprotective effects in several animal models [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

LC/ESI/TOF-MS Characterization, Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats

2022

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In this study, the attenuative effects of the hydro-alcoholic extract from Mitragyna speciosa (MSE) against diabetes-induced anxiety and depression-like behaviors were examined. In addition, UPLC/ESI/TOF-MS analysis was performed to identify the phytochemical nature of MSE. DM was induced using a combination of high fructose/streptozotocin, and the diabetic rats were treated with MSE (50 and 200 mg/kg) for 5 weeks. After treatment, the animals were subjected to a forced swim test, open field test and elevated plus-maze tests. Additionally, proinflammatory cytokines and oxidative stress parameters were evaluated in the brain tissues of the rats. UPLC/ESI/TOF-MS analysis revealed that MSE is abundantly rich in polyphenolic constituents, notably flavonoid and phenolic glycosides. Behavioral tests and biochemical analyses indicated that diabetic rats showed significantly increased anxiety and depressive-like behavioral deficits, brain oxidative stress and pro-inflammatory cytokines levels (IL-1β, IL-6 and TNF-α). Treatment with MSE (50 and 200 mg/kg) significantly attenuated increased blood glucose level, depressive and anxiety-like behaviors in diabetic rats. Additionally, the antioxidant enzymes activities were markedly increased in MSE-treated animals, while TNF-α, IL-1β and IL-6 cytokines were notably suppressed. Taken together, these results suggested that MSE has potentials as antidepressant and anxiolytic-like effects and improves the brain oxido-inflammatory status in diabetic rats.

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Isoliquiritigenin attenuates inflammation and modulates Nrf2/caspase-3 signalling in STZ-induced aortic injury

Cited by 14 publications

References 39 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

Paeoniflorin Protects H9c2 Cardiomyocytes against Hypoxia/Reoxygenation Induced Injury via Regulating the AMPK/Nrf2 Signaling Pathway

LC/ESI/TOF-MS Characterization, Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats

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