Hepatoprotective effect of esculetin on ethanol-induced liver injury in human HepG2 cells and C57BL/6J mice

Lee, Jaemin; Yang, Jinwoo; Jeon, Ji‐Young; Jeong, Heon Sang; Lee, Junsoo; Sung, Jeehye

doi:10.1016/j.jff.2017.11.024

Cited by 35 publications

(30 citation statements)

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“…Once within to the nucleus, Nrf2 binds to the cis ‐acting ARE within the promoters of antioxidant and detoxifying enzymes, which leads to the transcription of the target genes including antioxidant and detoxifying enzymes (Ge et al, ). It has been reported that Nrf2/ARE pathway plays a key role as a defense system to prevent the ALD development (Lee et al, ; Senthil Kumar et al, ). In this study, the effects of quercetin derivatives on Nrf2/ARE signaling pathways activation were examined by measuring the induction of antioxidant enzymes, Nrf2 nuclear translocation, and ARE‐driven promoter activity.…”

Section: Resultsmentioning

confidence: 99%

“…Human‐derived hepatic cell line (HepG2; Korean Collection for Type Cultures, Daejeon, Korea) was cultured in Dulbecco's modified Eagle medium (DMEM; Gibco, Thermo Fisher Scientific, Waltham, MA, USA) including 10% fetal bovine serum (FBS; (Gibco), 100 μg/ml streptomycin and 100 U/ml penicillin (Gibco) in 5% CO 2 at 37°C. Ethanol treatment was conducted as previously described (Lee et al, ). Briefly, the HepG2 cells were grown at high density (80% confluency) in 10% FBS‐DMEM at 37°C/5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Each tested sample was prepared by dissolving each compound in dimethyl sulfoxide (DMSO). Esculetin and silymarin were used as positive controls that have been reported to be effective against ethanol‐induced hepatotoxicity models (Lee et al, ; Song et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Under stress conditions, excessive ROS disrupts the Keap1–Nrf2 interactions, initiating an efficient nuclear translocation of Nrf2. The translocated Nrf2 binds to the antioxidant response element (ARE) and increases the antioxidant and detoxifying enzyme expression (Lee et al, ; Sykiotis & Bohmann, ). This suggests that the Nrf2/ARE pathway can be a therapeutic strategy for cellular detoxification against alcohol‐induced liver toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Relative protective activities of quercetin, quercetin‐3‐glucoside, and rutin in alcohol‐induced liver injury

Seyun

Lee

et al. 2019

J Food Biochem

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Alcoholic liver diseases has been known to be one of the major health risks worldwide. The purpose of this study was aimed to demonstrate the relative protective effect of quercetin, quercetin‐3‐glucoside, and rutin on alcohol‐induced damage in hepatocytes. The hepatotoxicity, antioxidant enzymatic defense mechanisms, and pro‐inflammatory mediators were examined for evaluating the hepatoprotective effects of quercetins in hepG2 cells. The results revealed that quercetin and its glucoside derivatives significantly prevented ethanol‐induced hepatotoxicity by decreasing hepatic aminotransferase activities and inflammatory response in HepG2 cells. Moreover, the quercetins significantly induced detoxifying enzymes via the nuclear accumulation of the NF‐E2‐related factor 2 (Nrf2) and induction of antioxidant response element (ARE) gene. These hepatoprotective activities were observed to be more effective with quercetin aglycone than quercetin glucosides. From the above findings, the present study imply that quercetin aglycone may have a vital function in the therapeutic and preventive strategies of alcoholic liver diseases. Practical applications Quercetin is commonly present in fruits and vegetables as aglycone and glucoside‐derived forms. In the present study, quercetin and its glycosides was shown to alleviate oxidative stress, glutathione depletion, and pro‐inflammatory cytokines in alcohol‐induced HepG2 cells via the Nrf2/ARE antioxidant pathway. Moreover, quercetin aglycone had better protective effects against alcohol‐induced liver damage in vitro, compared to its glycosylated form. The present study proposed that quercetin aglycone may be a more efficient hepatoprotective agent than its glucoside derivatives such as rutin in the amelioration of alcohol‐induced liver diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relative protective activities of quercetin, quercetin‐3‐glucoside, and rutin in alcohol‐induced liver injury

Seyun

Lee

et al. 2019

J Food Biochem

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“…The ROS detection results showed that the ROS expression of HepG2 cells increased after ethanol treatment; however, treatment with DIF can reduce the production of ROS and GGT proteins, increase the levels of SOD and GSH proteins, and reduce DNA damage. Research has proved that alcohol can lead to oxidative stress and the overexpression of ROS [11,39,40]. Overexpression of ROS induces apoptosis by activating caspase family proteins and other signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of the Polysaccharide Precursor, D-Isofloridoside, from Laurencia undulata on Alcohol-Induced Hepatotoxicity in HepG2 Cells

et al. 2020

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Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that have been attributed to polysaccharide precursors. D-Isofloridoside (DIF) is one of the polysaccharide precursors from the marine red alga Laurencia undulata. This study evaluated the effect of DIF on alcohol-induced oxidative stress in human hepatoma cells (HepG2). As a result, DIF attenuated alcohol-induced cytotoxicity, reduced the amount of intracellular reactive oxygen species (ROS), and effectively reduced alcohol-induced DNA damage in HepG2 cells. In addition, a western blot showed that, after DIF treatment, the expression levels of glutathione (GSH), superoxide dismutase (SOD), and B-cell lymphoma-2 (bcl-2) increased, while the expression levels of γ-glutamyl transferase (GGT), BCL2-associated X (bax), cleaved caspase-3, and mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase) signal transduction proteins reduced. This showed that DIF may protect cells by reducing the amount of intracellular ROS and inhibiting intracellular oxidative stress and apoptotic processes. Finally, molecular docking demonstrated that DIF can bind to SOD, GGT, B-cell lymphoma-2, and bax proteins. These results indicated that DIF can protect HepG2 cells from alcohol-induced oxidative stress damage, making it an effective potential ingredient in functional foods.

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Esculetin unveiled: Decoding its anti‐tumor potential through molecular mechanisms—A comprehensive review

Rezoan Hossain,

Zahra Shova,

Akter

et al. 2023

Cancer Reports

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BackgroundThe growing complexity of cancer has made it a significant concern in the medical community. Although cancer research has advanced, it is still challenging to create new effective medications due to the limitations and side effects of existing treatment strategies. These are enforcing the development of some alternative drugs from natural compounds with fewer drawbacks and side effects.AimTherefore, this review aims to provide up‐to‐date, crucial, and all‐encompassing data on esculetin's anticancer activity, including all relevant molecular and cellular processes based on in vivo and in vitro investigations.ResultsAccording to the literature review, esculetin is available in nature and is effective against 16 different types of cancer. The general mechanism shown by esculetin is modulating signaling cascades and its related pathways, like cell proliferation, cell growth, autophagy, apoptosis, necrosis, inflammation, angiogenesis, metastasis, invasion, and DNA damage. Nanoformulation of esculetin improves this natural product's efficacy by improving water solubility. Esculetin's synergistic effects with both natural substances and conventional treatments have been shown, and this method aids in reversing resistance mechanisms by modulating resistance‐related proteins. In addition, it has fewer side effects on humans than other phytochemicals and standard drugs with some good pharmacokinetic features.ConclusionTherefore, until standard chemotherapeutics are available in pharmaceutical markets, esculetin should be used as a therapeutic drug against various cancer types.

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Hepatoprotective effect of esculetin on ethanol-induced liver injury in human HepG2 cells and C57BL/6J mice

Cited by 35 publications

References 28 publications

Relative protective activities of quercetin, quercetin‐3‐glucoside, and rutin in alcohol‐induced liver injury

Relative protective activities of quercetin, quercetin‐3‐glucoside, and rutin in alcohol‐induced liver injury

The Protective Effect of the Polysaccharide Precursor, D-Isofloridoside, from Laurencia undulata on Alcohol-Induced Hepatotoxicity in HepG2 Cells

Esculetin unveiled: Decoding its anti‐tumor potential through molecular mechanisms—A comprehensive review

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