Ameliorative Effects of Dietary Ellagic Acid Against Severe Malaria Pathogenesis by Reducing Cytokine Storms and Oxidative Stress

Ellagic acid (EA), a fruit- and vegetable-derived flavonoid, has been reported for multiple pharmacological activities, which encouraged us to examine its useful effect in severe malaria pathogenesis, especially malaria-induced cytokine storms and oxidative stress linked to damage in major organs. Malaria was induced by injecting Plasmodium berghei–infected RBCs intraperitoneally into the mice. EA was given orally (5, 10, and 20 mg/kg) following Peter’s 4-day suppression test. EA exhibited the suppression of parasitemia, production of inflammatory cytokine storms and oxidative stress marker level quantified from vital organs significantly and an increase in hemoglobin, blood glucose, and mean survival time compared to the vehicle-treated infected group. EA administration also restored the blood–brain barrier integrity evidenced through Evans blue staining. Furthermore, we demonstrated the protecting effect of EA in LPS-induced inflammatory cytokine storms and oxidative stress in glial cells. The present study conclude that ellagic acid is able to alleviate severe malaria pathogenesis by reducing cytokine storms and oxidative stress–induced by malarial parasites. It also attributed promising antimalarial activity and afforded to improve the blood glucose and hemoglobin levels in treated mice. These research findings suggested the suitability of ellagic acid as a useful bioflavonoid for further study for the management of severe malaria pathogenesis.

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

Mediators of Inflammation ◽

10.1155/2021/6359652 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Huanjin Song ◽

Hao Wu ◽

Jun Dong ◽

Sihua Huang ◽

Jintao Ye ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Ellagic Acid ◽

Oxidative Stress Marker ◽

Dependent Manner ◽

Histone Deacetylase 1 ◽

Protein Levels ◽

Tnf Α ◽

And Oxidative Stress

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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Effects of probiotics on blood glucose, biomarkers of inflammation and oxidative stress in pregnant women with gestational diabetes mellitus: A meta-analysis of randomized controlled trials

Medicina Clínica ◽

10.1016/j.medcli.2019.05.041 ◽

2020 ◽

Vol 154 (6) ◽

pp. 199-206 ◽

Cited By ~ 3

Author(s):

Yuan Chen ◽

Rensong Yue ◽

Boxun Zhang ◽

Zhenhua Li ◽

Jiacheng Shui ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Blood Glucose ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Controlled Trials ◽

Randomized Controlled ◽

And Oxidative Stress

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Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers

Antioxidants ◽

10.3390/antiox10010114 ◽

2021 ◽

Vol 10 (1) ◽

pp. 114

Author(s):

Pahriya Ashrap ◽

Deborah J. Watkins ◽

Ginger L. Milne ◽

Kelly K. Ferguson ◽

Rita Loch-Caruso ◽

...

Keyword(s):

Oxidative Stress ◽

Prostaglandin F2α ◽

Urine Samples ◽

Oxidative Stress Marker ◽

Essential Metals ◽

Male Fetus ◽

Metal Concentrations ◽

Fetal Sex ◽

Wide Range ◽

And Oxidative Stress

Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

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Serum Prolidase Activity and Oxidative Stress in Diabetic Nephropathy and End Stage Renal Disease: A Correlative Study with Glucose and Creatinine

Biochemistry Research International ◽

10.1155/2014/291458 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 11

Author(s):

Akhilesh Kumar Verma ◽

Subhash Chandra ◽

Rana Gopal Singh ◽

Tej Bali Singh ◽

Shalabh Srivastava ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Blood Glucose ◽

Renal Disease ◽

Serum Creatinine ◽

End Stage Renal Disease ◽

Prolidase Activity ◽

Stage Renal Disease ◽

End Stage ◽

And Oxidative Stress

Association of oxidative stress and serum prolidase activity (SPA) has been reported in many chronic diseases. The study was aimed at evaluating the correlation of glucose and creatinine to SPA and oxidative stress in patients with diabetic nephropathy (DN) and end stage renal disease (ESRD) concerned with T2DM. 50 healthy volunteers, 50 patients with T2DM, 86 patients with DN, and 43 patients with ESRD were considered as control-1, control-2, case-1, and case-2, respectively. Blood glucose, creatinine, SPA, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured by colorimetric tests. SPA, TOS, and OSI were significantly increased in case-1 and case-2 than control-1 and control-2, while TAS was significantly decreased(P<0.001). Blood glucose was linearly correlated to SPA, TOS, TAS, and OSI in control-2, case-1 and case-2(P<0.001). Serum creatinine was linearly correlated with SPA, TOS, TAS and OSI in control-2 and case-1(P<0.001). In case-2, serum creatinine was significantly correlated with SPA only(P<0.001). Thus, the study concluded that SPA and oxidative stress significantly correlated with blood glucose and creatinine. SPA, TOS, TAS, and OSI can be used as biomarkers for diagnosis of kidney damage.

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Role of the Lipoperoxidation Product 4-Hydroxynonenal in the Pathogenesis of Severe Malaria Anemia and Malaria Immunodepression

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/638416 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

Evelin Schwarzer ◽

Paolo Arese ◽

Oleksii A. Skorokhod

Keyword(s):

Oxidative Stress ◽

Severe Malaria ◽

Chemical Properties ◽

Oxidative Stress Marker ◽

Pathogenic Factor ◽

Biologically Relevant ◽

Cell Functions ◽

Low Concentrations ◽

Covalent Conjugates

Oxidative stress plays an important role in the pathogenesis offalciparummalaria, a disease still claiming close to 1 million deaths and 200 million new cases per year. Most frequent complications are severe anemia, cerebral malaria, and immunodepression, the latter being constantly present in all forms of malaria. Complications are associated with oxidative stress and lipoperoxidation. Its final product 4-hydroxynonenal (4-HNE), a stable yet very reactive and diffusible molecule, forms covalent conjugates with proteins, DNA, and phospholipids and modulates important cell functions at very low concentrations. Since oxidative stress plays important roles in the pathogenesis of severe malaria, it appears important to explore the role of 4-HNE in two important malaria complications such as malaria anemia and malaria immunodepression where oxidative stress is considered to be involved. In this review we will summarize data about 4-HNE chemistry, its biologically relevant chemical properties, and its role as regulator of physiologic processes and as pathogenic factor. We will review studies documenting the role of 4-HNE in severe malaria with emphasis on malaria anemia and immunodepression. Data from other diseases qualify 4-HNE both as oxidative stress marker and as pathomechanistically important molecule. Further studies are needed to establish 4-HNE as accepted pathogenic factor in severe malaria.

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