Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways

Chen, Kung Yen; Lin, Jui-An; Yao, Han; Hsu, An Chih; Tai, Yu Ting; Tai, Ying Hsuan; Hsieh, Mao Chih; Shen, Tang‐Long; Hsu, Ren Yi; Wu, Hong; Wang, Guey Horng; Ho, Bing Ying; Chen, Yu-Pei

doi:10.1016/j.nutres.2018.02.004

Cited by 10 publications

(5 citation statements)

References 50 publications

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“…Arctigenin also attenuated apoptosis, inflammation, and oxidative stress in oxygen glucose deprivation-treated cardiomyocytes, improved the heart functions and decreased the infarct size in the acute MI/R-rats [ 87 , 155 ]. On the normal WRL68 hepatocytes exposed to oleic acid accumulation, arctigenin demonstrated a protective effect on cell survival, lipid metabolism, oxidation stress, and inflammation [ 85 ]. Arctigenin mitigated cadmium-induced nephrotoxicity in rats by increasing GSH level and antioxidant enzyme activity providing protection against oxidative DNA damage [ 157 ].…”

Section: Lignans With Antioxidant and Anti-inflammatory Actionmentioning

confidence: 99%

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

Osmakov

Kalinovskii

Belozerova

et al. 2022

IJMS

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Plant lignans exhibit a wide range of biological activities, which makes them the research objects of potential use as therapeutic agents. They provide diverse naturally-occurring pharmacophores and are available for production by chemical synthesis. A large amount of accumulated data indicates that lignans of different structural groups are apt to demonstrate both anti-inflammatory and antioxidant effects, in many cases, simultaneously. In this review, we summarize the comprehensive knowledge about lignan use as a bioactive agent in disorders associated with oxidative stress and inflammation, pharmacological effects in vitro and in vivo, molecular mechanisms underlying these effects, and chemical synthesis approaches. This article provides an up-to-date overview of the current data in this area, available in PubMed, Scopus, and Web of Science databases, screened from 2000 to 2022.

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Section: Lignans With Antioxidant and Anti-inflammatory Actionmentioning

confidence: 99%

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

Osmakov

Kalinovskii

Belozerova

et al. 2022

IJMS

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“…These cells exhibit greater sensitivity to drug-induced steatosis [ 78 ] and features of MAFLD upon treatment with free fatty acids [ 79 ]. Other immortalized hepatic cell lines, such as fetal liver-derived WRL-68 and HCC-derived Huh7 cells, are also used in MAFLD modeling ( Table 1 ) [ 69 , 76 , 77 ]. All these immortalized cell lines have provided a simple approach to modeling the disease, and the ease of culture and high cell viability have made them excellent cell options for engineering approaches to create more complex cellular models.…”

Section: Human Immortalized and Primary Cell Lines For Modeling Mafldmentioning

confidence: 99%

Advancements in MAFLD Modeling with Human Cell and Organoid Models

Wang

Yan

Chan

2022

IJMS

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Metabolic (dysfunction) associated fatty liver disease (MAFLD) is one of the most prevalent liver diseases and has no approved therapeutics. The high failure rates witnessed in late-phase MAFLD drug trials reflect the complexity of the disease, and how the disease develops and progresses remains to be fully understood. In vitro, human disease models play a pivotal role in mechanistic studies to unravel novel disease drivers and in drug testing studies to evaluate human-specific responses. This review focuses on MAFLD disease modeling using human cell and organoid models. The spectrum of patient-derived primary cells and immortalized cell lines employed to model various liver parenchymal and non-parenchymal cell types essential for MAFLD development and progression is discussed. Diverse forms of cell culture platforms utilized to recapitulate tissue-level pathophysiology in different stages of the disease are also reviewed.

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“…The cell was cultured in DMEM supplemented with 10% FBS and 1% penicillinstreptomycin at 37°C in an incubator supplied with 5% CO 2 . Cells between passages 10 and 20 were used for assay (Chen et al, 2018).…”

Section: Cell Culturementioning

confidence: 99%

WRL-68 with the overexpression of CYP3A4 as an in vitro model to assess drug–drug interaction

Nurliana¹,

Normala²

2021

J Appl Pharm Sci

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The drawback of using hepatoma cell lines such as HepG2 instead of the "gold standard" primary hepatocytes in studying in vitro drug metabolism is that the phase I metabolism enzymes, cytochrome P450 (CYP450), are poorly expressed with lower activities. The accuracy of predicting drug metabolism and interactions could be jeopardized with these limitations. Human hepatic cell line WRL-68 exhibits similar morphology with hepatic primary cultures and is highly potential to be developed as an in vitro tool for metabolism-based study. This study aims to develop the CYP3A4 overexpression in vitro cell-based model as an efficient tool for drug metabolism and interactions study. WRL-68 exhibits optimum liver marker gene expression and is most suitable for the overexpression model compared to HepG2 and Chang liver cell lines. CYP3A4 overexpression in the transiently transfected cell model was measured using quantitative real-time PCR. Over 2000-fold, CYP3A4 expression was achieved 48 hours after transfection and Western blot analysis further confirmed CYP3A4 overexpression. In addition, CYP450 reductase and cytochrome b5 expression in the cell model which are vital for CYP3A4 catalytic activity were found to remain intact after CYP3A4 overexpression. This model was also optimized for its testosterone 6β-hydroxylation activity (K m : 20.60 ± 0.10 µM; V max : 43.23 ± 1.21 nM/minutes/mg total protein) and thus proven to be a useful tool for in vitro drug metabolism and interaction study involving CYP3A4.

show abstract

Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways

Cited by 10 publications

References 50 publications

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

Advancements in MAFLD Modeling with Human Cell and Organoid Models

WRL-68 with the overexpression of CYP3A4 as an in vitro model to assess drug–drug interaction

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