Recent Advances in the Production and Applications of Ellagic Acid and Its Derivatives. A Review

Evtyugin, Dmitry D.; Magina, Sandra; Evtuguin, Dmitry V.

doi:10.3390/molecules25122745

Cited by 121 publications

(86 citation statements)

References 136 publications

(171 reference statements)

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“… 22 ETs are hydrolyzed in the gut to release ellagic acid (EA), which is further processed by the microflora into urolithins through the loss of one of its two lactones and by successive removal of hydroxyl groups. 23 In the species investigated to date (including humans), urolithin A (UA), urolithin B (UB), urolithin C (UC) and urolithin D (UD) are the redundant measurable metabolites that are considered to be the end-products of both ETs and EA. 24 Many studies suggest that urolithin A (UA) is the main functional substance in antioxidant and anti-inflammatory activities after the body consumes foods rich in ellagitannin or ellagic acid.…”

Section: Introductionmentioning

confidence: 99%

Urolithin A Inhibits Epithelial–Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway

Cheng¹,

Dou²,

Zhang³

et al. 2021

OTT

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The epithelial-to-mesenchymal transition (EMT) is a fundamental process in tumor progression that endows cancer cells with migratory and invasive potential. Snail, a zinc finger transcriptional repressor, plays an important role in the induction of EMT by directly repressing the key epithelial marker E-cadherin. Here, we assessed the effect of urolithin A, a major metabolite from pomegranate ellagitannins, on Snail expression and EMT process. Methods: The role of Snail in urolithin A-induced EMT inhibition in lung cancer cells was explored by wound healing assay and cell invasion assay. The qRT-PCR and CHX assay were performed to investigate how urolithin A regulates Snail expression. Immunoprecipitation assays were established to determine the effects of urolithin A in mdm2-Snail interaction. In addition, the expression of p53 was manipulated to explore its effect on the expression of mdm2 and Snail. Results: The urolithin A dose-dependently upregulated epithelial marker and decreased mesenchymal markers in lung cancer cells. In addition, exposure to urolithin A decreased cell migratory and invasive capacity. We have further demonstrated that urolithin A inhibits lung cancer cell EMT by decreasing Snail protein expression and activity. Mechanistically, urolithin A disrupts the interaction of p53 and mdm2 which leads Snail ubiquitination and degradation. Conclusion:We conclude that urolithin A could inhibit EMT process by controlling mainly Snail expression. These results highlighted the role of pomegranate in regulation of EMT program in lung cancer.

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Section: Introductionmentioning

confidence: 99%

Urolithin A Inhibits Epithelial–Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway

Cheng¹,

Dou²,

Zhang³

et al. 2021

OTT

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“…Berry juices significantly enhance the growth of acrylamide-exposed yeast cells, and decreased the level of ROS [14]. Ellagic acid (EA) as a plant-derived natural product found in pomegranate (Punica granatum) and the family of ellagitannins (ETs) has different pharmacological effects [15]. Ellagic acid has generated a noticeable scientific interest because of beneficial health effects against many oxidative-linked diseases, including neurodegenerative and cancer diseases [15].…”

Section: Introductionmentioning

confidence: 99%

“…Ellagic acid (EA) as a plant-derived natural product found in pomegranate (Punica granatum) and the family of ellagitannins (ETs) has different pharmacological effects [15]. Ellagic acid has generated a noticeable scientific interest because of beneficial health effects against many oxidative-linked diseases, including neurodegenerative and cancer diseases [15]. It has been reported that ellagic acid can prevent of oxidative stress, inflammation, and histopathological alterations in acrylamide-induced hepatotoxicity in wistar rats [16].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial, lysosomal and DNA damages induced by acrylamide attenuate by ellagic acid in human lymphocyte

et al. 2021

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Acrylamide (AA), is an important contaminant formed during food processing under high temperature. Due to its potential neurotoxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, genotoxicity and carcinogenicity effects, this food contaminant has been recognized as a human health concern. Previous studies showed that acrylamide-induced toxicity is associated with active metabolite of acrylamide by cytochrome P450 enzyme, oxidative stress, mitochondrial dysfunction and DNA damage. In the current study, we investigated the role of oxidative stress in acrylamide’s genotoxicity and therapeutic potential role of ellagic acid (EA) in human lymphocytes. Human lymphocytes were simultaneously treated with different concentrations of EA (10, 25 and 50 μM) and acrylamide (50 μM) for 4 h at 37°C. After 4 hours of incubation, the toxicity parameters such cytotoxicity, ROS formation, oxidized/reduced glutathione (GSH/GSSG) content, malondialdehyde (MDA) level, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were analyzed using biochemical and flow cytometry evaluations. It has been found that acrylamide (50 μM) significantly increased cytotoxicity, ROS formation, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage in human lymphocytes. On the other hand, cotreatment with EA (25 and 50 μM) inhibited AA-induced oxidative stress which subsequently led to decreasing of the cytotoxicity, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage. Together, these results suggest that probably the co-exposure of EA with foods containing acrylamide could decrease mitochondrial, lysosomal and DNA damages, and oxidative stress induced by acrylamide in human body.

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“…Herein, we also explored whether ellagic acid (EA), as a natural antioxidant polyphenol, served as a potential therapeutic drug to attenuate SCH‐induced abnormal glucose metabolism in mice. EA is a dimeric derivative of gallic acid and extensively excavated in natural nutriments (Evtyugin & Magina, 2020). Numerous evidence indicate that EA is a super bioactive molecule to perform multiple biomedical applications, including anti‐inflammatory, antibacterial, anti‐oxidative, and anticancer activities (Alfei et al., 2020; Baradaran Rahimi et al., 2020; Evtyugin & Magina, 2020).…”

Section: Introductionmentioning

confidence: 99%

Subclinical hypothyroidism contributes to poor glycemic control in patients with type 2 diabetes mellitus, and ellagic acid attenuates methimazole‐induced abnormal glucose metabolism in mice model

Liu

Zhu

et al. 2021

J. Food Biochem.

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Subclinical hypothyroidism (SCH) as mild thyroid disorder or comorbidity in patients with endocrine disorders is closely related with insulin resistance (IR) and poor glycemic control. The present study attempted to investigate the effect of SCH on IR and glycemic control in patients with type 2 diabetes mellitus (T2DM). In addition, the effects of ellagic acid (EA) on SCH C57BL/6J and db/db mice were also investigated to explore potential therapeutic drug against SCH‐induced abnormal glucose metabolism. T2DM patients were recruited in our study and categorized into two groups according to thyroid stimulating hormone (TSH) value: T2DM without SCH group (TSH ≤4 μIU/ml; n = 30) and T2DM with SCH group (TSH >4μIU/ml; n = 60). Methimazole (MMI; 0.08 mg kg−1 day−1) was intragastrically administrated for 12 weeks to establish SCH in C57BL/6J and db/db mice. Compared with T2DM patients without SCH, poor glycemic and cholesterol control were emerged in T2DM patients with SCH and that were prominent in patients with TSH more than 10 μIU/ml. In addition, a significant positive correlation between serum TSH and fasting plasma‐glucose (FPG), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), or glycated hemoglobin (HbA1c) was observed in T2DM patients with SCH. Moreover, abnormal glucose metabolism in C57BL/6J and db/db mice with SCH has been attenuated by EA administration. Our findings provided data regarding the positive correlation between high TSH level with poor glycemic control in T2DM patients with SCH. EA might be a supportive strategy for preventing SCH‐induced abnormal glucose metabolism. Practical applications Subclinical hypothyroidism (SCH) is a potential risk factor associated with abnormal glucose metabolism in patients with type 2 diabetes mellitus (T2DM). A clinical theory of a positive correlation between high TSH level and poor glycemic control was validated in type 2 diabetes mellitus patients and mouse models. Ellagic acid (EA) might be a supportive strategy for preventing SCH‐induced abnormal glucose metabolism that provided a treatment option in T2DM patients with subclinical hypothyroidism in clinical practice.

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Recent Advances in the Production and Applications of Ellagic Acid and Its Derivatives. A Review

Cited by 121 publications

References 136 publications

Urolithin A Inhibits Epithelial–Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway

Urolithin A Inhibits Epithelial–Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway

Mitochondrial, lysosomal and DNA damages induced by acrylamide attenuate by ellagic acid in human lymphocyte

Subclinical hypothyroidism contributes to poor glycemic control in patients with type 2 diabetes mellitus, and ellagic acid attenuates methimazole‐induced abnormal glucose metabolism in mice model

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