Epigallocatechin-3-gallate prevents TNF-α-induced NF-κB activation thereby upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells

Jiang, Jun; Zhang, Mo; Yin, Kai; Zhao, Guo-Jun; Lv, Yun-Cheng; Ouyang, Xin; Jiang, Zhi‐Sheng; Fu, Yue; Tang, Chao-Ke

doi:10.3892/ijmm.2012.924

Cited by 41 publications

(27 citation statements)

References 48 publications

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“…The infliximab concentration used in this study is within the therapeutic range for RA and is close to the average trough level of 3.3 μ g/mL [19, 20]. Our finding that TNF- α decreases ABCA1 and LXR- α is consistent with previous reports in macrophages and other cell types [21–24].…”

Section: Resultssupporting

confidence: 91%

Infliximab Reverses Suppression of Cholesterol Efflux Proteins by TNF-α: A Possible Mechanism for Modulation of Atherogenesis

Voloshyna

Seshadri

Anwar

et al. 2014

BioMed Research International

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Tumor necrosis factor- (TNF-) α is a proinflammatory proatherogenic cytokine. Infliximab, an anti-TNF-α monoclonal antibody, is effective in treating rheumatoid arthritis. However, its impact on cardiovascular burden and lipid transport is unclear. The present study investigates the effect of TNF-α and infliximab on reverse cholesterol transport (RCT) proteins. Uptake of modified lipoproteins by macrophages in the vasculature leads to atherogenic foam cell formation. RCT is mediated by proteins including ATP binding cassette transporters A1 (ABCA1), G1 (ABCG1), liver X receptor- (LXR-) α, and 27-hydroxylase. RCT counteracts lipid overload by ridding cells of excess cholesterol. THP-1 human monocytes were incubated with either TNF-α alone or TNF-α with infliximab. Expression of proteins involved in cholesterol efflux was analyzed. TNF-α significantly reduced both ABCA1 and LXR-α mRNA (to 68.5 ± 1.59%, P < 0.05, and 41.2 ± 0.25%, P < 0.01, versus control set as 100%, resp.). Infliximab nullified the TNF-α effect. Results were confirmed by Western blot. Infliximab abolished the increase in foam cells induced by TNF-α. TNF-α treatment significantly reduces ABCA1 and LXR-α expression in monocytes, thus bringing about a proatherogenic state. The anti-TNF drug infliximab, commonly used in rheumatology, restored RCT proteins. This is the first report of an atheroprotective effect of infliximab on RCT in monocytes.

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Section: Resultssupporting

confidence: 91%

Infliximab Reverses Suppression of Cholesterol Efflux Proteins by TNF-α: A Possible Mechanism for Modulation of Atherogenesis

Voloshyna

Seshadri

Anwar

et al. 2014

BioMed Research International

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“…Although previous studies showed that SFN activated NRF2 and ameliorated diabetes-induced testicular apoptotic cell death without knowing the expression of Keap1 [5, 6], we speculate that inhibition of KEAP1 function by SFN could be the mechanism through which SFN activated NRF2 in these studies. Similar to SFN, EGCG is also known to activate NRF2 by inactivating KEAP1 [46, 47]. EGCG is speculated to directly interact with the cysteine residues present in KEAP1, thereby stimulating NRF2 dissociation from KEAP1 [48].…”

Section: Discussionmentioning

confidence: 99%

NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic Testicular Damage

Pan

Zhou

et al. 2017

Oxidative Medicine and Cellular Longevity

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Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found to ameliorate diabetic testicular damage (DTD) in rodents. However, it was unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on multiple diabetic complications. However, the effect of EGCG has not been studied in DTD. The present study aims to explore the role of NRF2 in both self and EGCG protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced loss in testicular weight and spermatozoa count, and increase in testicular apoptotic cell death, as compared with the WT mice. EGCG activated NRF2 expression and function, preserved testicular weight and spermatozoa count, and attenuated testicular apoptotic cell death, endoplasmic reticulum stress, inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO diabetic mice. The present study demonstrated for the first time that NRF2 plays a critical role in both self and EGCG protection against DTD.

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“…Because of our recently reported effects of inflammation on UFs26 and possible anti-inflammatory effects of EGCG,27,28 we assessed specific markers of inflammation in all participants. We measured the levels of two serum inflammation biomarkers (interleukin 6 and tumor necrosis factor-α)29,30 and one urinary biomarker (isoprostane)31 of inflammation. All participants underwent endometrial biopsy at baseline (visit 1) and at the end of the study after 4 months (visit 5) to confirm the presence of normal endometrium and to ensure the safety of EGCG treatment on endometrium histology 32,33.…”

Section: Methodsmentioning

confidence: 99%

Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study

Roshdy¹,

Rajaratnam²,

Maitra³

et al. 2013

IJWH

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BackgroundUterine fibroids (UFs, also known as leiomyoma) affect 70% of reproductive-age women. Imposing a major burden on health-related quality-of-life (HRQL) of premenopausal women, UF is a public health concern. There are no effective medicinal treatment options currently available for women with symptomatic UF.ObjectivesTo evaluate the efficacy and safety of green tea extract (epigallocatechin gallate [EGCG]) on UF burden and quality of life in women with symptomatic UF, in a double-blinded, placebo-controlled randomized clinical trial.MethodsA total of 39 reproductive-age women (age 18–50 years, day 3 serum follicle-stimulating hormone <10 \U/mL) with symptomatic UF were recruited for this study. All subjects had at least one fibroid lesion 2 cm3 or larger, as confirmed by transvaginal ultrasonography. The subjects were randomized to oral daily treatment with either 800 mg of green tea extract (45% EGCG) or placebo (800 mg of brown rice) for 4 months, and UF volumes were measured at the end, also by transvaginal ultrasonography. The fibroid-specific symptom severity and HRQL of these UF patients were scored at each monthly visit, using the symptom severity and quality-of-life questionnaires. Student’s t-test was used to evaluate statistical significance of treatment effect between the two groups.ResultsOf the final 39 women recruited for the study, 33 were compliant and completed all five visits of the study. In the placebo group (n = 11), fibroid volume increased (24.3%) over the study period; however, patients randomized to green tea extract (n = 22, 800 mg/day) treatment showed significant reduction (32.6%, P = 0.0001) in total UF volume. In addition, EGCG treatment significantly reduced fibroid-specific symptom severity (32.4%, P = 0.0001) and induced significant improvement in HRQL (18.53%, P = 0.01) compared to the placebo group. Anemia also significantly improved by 0.7 g/dL (P = 0.02) in the EGCG treatment group, while average blood loss significantly decreased from 71 mL/month to 45 mL/month (P = 0.001). No adverse effects, endometrial hyperplasia, or other endometrial pathology were observed in either group.ConclusionEGCG shows promise as a safe and effective therapeutic agent for women with symptomatic UFs. Such a simple, inexpensive, and orally administered therapy can improve women’s health globally.

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Epigallocatechin-3-gallate prevents TNF-α-induced NF-κB activation thereby upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells

Cited by 41 publications

References 48 publications

Infliximab Reverses Suppression of Cholesterol Efflux Proteins by TNF-α: A Possible Mechanism for Modulation of Atherogenesis

Infliximab Reverses Suppression of Cholesterol Efflux Proteins by TNF-α: A Possible Mechanism for Modulation of Atherogenesis

NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic Testicular Damage

Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study

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