Apigenin Alleviates Endotoxin‐Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy

Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chengkai; Hao, Enkui

doi:10.1155/2017/2302896

Cited by 67 publications

(49 citation statements)

References 67 publications

(72 reference statements)

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“…Earlier research reported the effect of API on autophagy. Fang et al found that API promoted autophagy and alleviated myocardial oxidative and inflammatory injury, and endotoxininduced myocardial toxicity (Li et al, 2017). Additionally, API plays an anti-tumor role by promoting autophagy in various tumors such as skin cancer (Bridgeman et al, 2016), colon cancer (Lee et al, 2014;Chen et al, 2019), thyroid carcinoma (Zhang et al, 2015), and hepatocellular carcinoma (Gao et al, 2018;Yang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway

Zhao

Zhang

et al. 2020

Front. Pharmacol.

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Acetaminophen (APAP) overdose is the main cause of acute liver failure. Apigenin (API) is a natural dietary flavonol with high antioxidant capacity. Herein, we investigated protection by API against APAP-induced liver injury in mice, and explored the potential mechanism. Cell viability assays and mice were used to evaluate the effects of API against APAPinduced liver injury. Western blotting, immunofluorescence staining, RT-PCR, and Transmission Electron Microscope were carried out to determine the signalling pathways affected by API. Analysis of mouse serum levels of alanine/aspartate aminotransferase (ALT/AST), malondialdehyde (MDA), liver myeloperoxidase (MPO) activity, glutathione (GSH), and reactive oxygen species (ROS) revealed that API (80 mg/kg) owned protective effect on APAP-induced liver injury. Meanwhile, API ameliorated the decreased cell viability in L-02 cells incubated by APAP with a dose dependent. Furthermore, API promoted SIRT1 expression and deacetylated p53. Western blotting showed that API promoted APAP-induced autophagy, activated the NRF2 pathway, and inhibited the transcriptional activation of nuclear p65 in the presence of APAP. Furthermore, SIRT1 inhibitor EX-527 reduced protection by API against APAP-induced hepatotoxicity. Molecular docking results indicate potential interaction between API and SIRT1. API prevents APAP-induced liver injury by regulating the SIRT1-p53 axis, thereby promoting APAP-induced autophagy and ameliorating APAP-induced inflammatory responses and oxidative stress injury.

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Section: Discussionmentioning

confidence: 99%

Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway

Zhao

Zhang

et al. 2020

Front. Pharmacol.

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“…They established that apigenin can promote ABCC1-mediated glutathione efflux from P. falciparum infected erythrocytes and impede parasite proliferation. In the cardiovascular system, Li et al [44] found that apigenin can protect against endotoxininduced myocardial injury and improve cardiac function by regulating oxidative stress and inflammation in vivo. In myocardial ischemia/reperfusion (I/R) mice, treatment with apigenin decreased infarct size and the release of lactate dehydrogenase (LDH) and creatine kinase (CK).…”

Section: Discussionmentioning

confidence: 99%

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Ren

Jiang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4’, 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE^-/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE^-/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE^-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation.

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“…Apigenin (AP) is a bioactive flavonoid which is obtained from several fruits and vegetables. AP has been reported to exhibit antioxidant, anti-inflammatory, and anticancer activities [16,17]. Our previous study has shown that AP exhibited protective effects on ARPE-19 cells against tert-butyl hydroperoxide-(t-BHP-) induced oxidative injury, which were associated with its antioxidant properties dependent upon the activation of Nrf2 signaling [18].…”

Section: Introductionmentioning

confidence: 99%

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Zhang

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a critical factor in the pathology of age-related macular degeneration (AMD). Apigenin (AP) is a flavonoid with an outstanding antioxidant activity. We had previously observed that AP protected APRE-19 cells against oxidative injury in vitro. However, AP has poor water and fat solubility, which determines its low oral bioavailability. In this study, we prepared the solid dispersion of apigenin (AP-SD). The solubility and dissolution of AP-SD was significantly better than that of the original drug, so the oral bioavailability in rats was better than that of the original drug. Then, the effects of AP-SD on the retina of a model mouse with dry AMD were assessed by fundus autofluorescence (FAF), optical coherence tomography (OCT), and electron microscopy; the results revealed that AP-SD alleviated retinopathy. Further research found that AP-SD promoted the nuclear translocation of Nrf2 and increased expression levels of the Nrf2 and target genes HO-1 and NQO-1. AP-SD enhanced the activities of SOD and GSH-Px and decreased the levels of ROS and MDA. Furthermore, AP-SD upregulated the expressions of p62 and LC3II in an Nrf2-dependent manner. However, these effects of AP-SD were observed only in the retina of Nrf2 WT mice, not in Nrf2 KO mice. In addition, the therapeutic effect of AP-SD was dose dependent, and AP did not work. In conclusion, AP-SD significantly enhanced the bioavailability of the original drug and reduced retinal oxidative injury in the model mouse of dry AMD in vivo. The results of the underlying mechanism showed that AP-SD upregulated the expression of antioxidant enzymes through the Nrf2 pathway and upregulated autophagy, thus inhibiting retinal oxidative damage. AP-SD may be a potential compound for the treatment of dry AMD.

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Apigenin Alleviates Endotoxin‐Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy

Cited by 67 publications

References 67 publications

Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway

Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

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