Ellagic Acid Ameliorates Lung Inflammation and Heart Oxidative Stress in Elastase-Induced Emphysema Model in Rat

Mansouri, Zahra; Dianat, Mahin; Radan, Maryam; Badavi, Mohammad

doi:10.1007/s10753-020-01201-4

Cited by 28 publications

(17 citation statements)

References 36 publications

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“…The natural polyphenol EA has been reported to have antioxidant, anti-inflammatory, and anticancer biological activities. EA prevented the development of lung and heart injuries though ameliorating lung inflammation and heart oxidative stress in elastase-induced emphysema model in rats [ 18 ]. Interestingly, it was previously reported that EA alleviated adjuvant induced arthritis in the mouse model mice by downregulation of proinflammatory cytokines and upregulation of anti-inflammatory cytokines [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

Song

Dong

et al. 2021

Mediators of Inflammation

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Ellagic acid (EA) was reported to play protective roles in rheumatoid arthritis (RA). It was found that the level of metastasis-associated gene 1 (MTA1)/histone deacetylase 1 (HDAC1) protein complex was downregulated by polyphenols in several human disorders. Notably, inhibition of MTA1 or HDAC1 has anti-inflammatory effects on RA. Therefore, our study is aimed at investigating whether EA prevents RA progression through regulating the MTA1/HDAC1 complex. Herein, the human fibroblast-like synoviocyte (FLS) cell line MH7A was treated with TNF-α to induce an inflammation model in vitro and then incubated with different concentrations of EA. Western blot analysis showed that EA reduced MTA1 expression in a dose-dependent manner in MH7A cells. Then, TNF-α-treated MH7A cells were incubated with EA alone or together with MTA1 overexpression plasmid (pcDNA-MTA1), and we found that EA inhibited proliferation, inflammation cytokine levels, and oxidative stress marker protein levels and promoted apoptosis in MH7A cells, while MTA1 overexpression abolished these effects. Moreover, coimmunoprecipitation assay verified the interaction between MTA1 and HDAC1. EA downregulated the MTA1/HDAC1 complex in MH7A cells. MTA1 knockdown inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells, while HDAC1 overexpression reversed these effects. Moreover, chromatin immunoprecipitation assay indicated that EA inhibited HDAC1-mediated Nur77 deacetylation. Rescue experiments demonstrated that Nur77 knockdown reversed the effects of EA on MH7A cell biological behaviors. Additionally, EA treatment attenuated arthritis index, paw swelling, synovial hyperplasia, and inflammation in collagen-induced arthritis (CIA) rats. In conclusion, EA inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells and alleviated the severity of RA in CIA rats though downregulating MTA1/HDAC1 complex and promoting HDAC1 deacetylation-mediated Nur77 expression.

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Section: Discussionmentioning

confidence: 99%

Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

Song

Dong

et al. 2021

Mediators of Inflammation

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“…Sulforaphane upregulates the expression of Nrf2 and its downstream gene NQO1 and reduces SuHx-induced pulmonary vascular remodeling, inflammation, and fibrosis [62]. As a natural antioxidant, ellagic acid has a protective effect on PAH and lung and heart injury in SD rats caused by porcine pancreatic elastase, which reduces antioxidant levels [63]. Oral melatonin administered to maternal sheep in the late gestation period improved the pulmonary vascular function of plateau PAH lambs, enhanced antioxidant capacity, and reduced the production of ROS and nitrotyrosine, a marker of oxidative stress in small pulmonary vessels [64,65].…”

Section: Latest Strategies For Oxidative Stress In Pah 821 Preclinica...mentioning

confidence: 99%

Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension

Gou

et al. 2022

Molecules

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Pulmonary arterial hypertension (PAH) is clinically characterized by a progressive increase in pulmonary artery pressure, followed by right ventricular hypertrophy and subsequently right heart failure. The underlying mechanism of PAH includes endothelial dysfunction and intimal smooth muscle proliferation. Numerous studies have shown that oxidative stress is critical in the pathophysiology of PAH and involves changes in reactive oxygen species (ROS), reactive nitrogen (RNS), and nitric oxide (NO) signaling pathways. Disrupted ROS and NO signaling pathways cause the proliferation of pulmonary arterial endothelial cells (PAECs) and pulmonary vascular smooth muscle cells (PASMCs), resulting in DNA damage, metabolic abnormalities, and vascular remodeling. Antioxidant treatment has become a main area of research for the treatment of PAH. This review mainly introduces oxidative stress in the pathogenesis of PAH and antioxidative therapies and explains why targeting oxidative stress is a valid strategy for PAH treatment.

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“…57 In emphysema models, ellagic acid, as a natural antioxidant, has a protective effect against pulmonary hypertension and the development of lung and heart damage induced by elastase. 58 Luteolin, a natural flavonoid, can treat COPD by altering the M1/M2 polarization of macrophages, thereby exerting anti-inflammatory effects through downregulation of p-STAT3 and upregulation of p-STAT6, 59 as well as through ERK-mediated inflammation, apoptosis, and autophagy inhibition. 60 Salvianolic acid b has been investigated as an anti-emphysema agent with the ability to reverse alveolar structural damage/loss and inhibit induced lung cell death through JAK2/STAT3/VEGF-dependent stimulation of lung cell proliferation and migration.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

Lin

Zhang

et al. 2022

Natural Product Communications

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Xuebijing injection (XBJ), one of the classical prescriptions for treating inflammation-related diseases, has been used to chronic obstructive pulmonary disease (COPD) in clinical practice. However, its molecular mechanism is still unclear. Network pharmacology combined with Affymetrix arrays and molecular docking techniques were applied to explore the molecular mechanism of XBJ for COPD. Predictive analysis of 728 active compounds in XBJ and 6 sets of Affymetrix arrays expression data resulted in 106 potential therapeutic targets. Next, based on the active compound-co-target network topology analysis, most of these targets were found to be modulated by quercetin, myricetin, and ellagic acid. Furthermore, protein–protein interaction (PPI) analysis revealed that the key targets may be EGFR, STAT3, AKT1, CCND1, MMP9, AR, ESR1, and PTGS2. Then, by constructing a component-target-pathway network, we found that XBJ was a multi-pathway, multi-target, multi-compound synergistic therapy for COPD, and four key targets were involved in the FoxO signaling pathway. Luteolin and salvianolic acid b had the optimal binding ability to several key proteins. Therefore, we hypothesize that quercetin, myricetin, ellagic acid, luteolin, and salvianolic acid b mainly contribute to the therapeutic effect of XBJ on COPD by modulating the FoxO signaling pathway by regulating EGFR, STAT3, AKT1, and CCND1. XBJ exerts anti-inflammatory and antioxidative stress effects through the PI3K/Akt/FoxO axis combined with MMP9, AR, ESR1, and PTGS2 to regulate other signaling pathways.

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Ellagic Acid Ameliorates Lung Inflammation and Heart Oxidative Stress in Elastase-Induced Emphysema Model in Rat

Cited by 28 publications

References 36 publications

Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

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