Kaempferol and Kaempferide Attenuate Oleic Acid-Induced Lipid Accumulation and Oxidative Stress in HepG2 Cells

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases which lacks ideal treatment options. Kaempferol and kaempferide, two natural flavonol compounds isolated from Hippophae rhamnoides L., were reported to exhibit a strong regulatory effect on lipid metabolism, for which the mechanism is largely unknown. In the present study, we investigated the effects of kaempferol and kaempferide on oleic acid (OA)-treated HepG2 cells, a widely used in vitro model of NAFLD. The results indicated an increased accumulation of lipid droplets and triacylglycerol (TG) by OA, which was attenuated by kaempferol and kaempferide (5, 10 and 20 μM). Western blot analysis demonstrated that kaempferol and kaempferide reduced expression of lipogenesis-related proteins, including sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1). Expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding proteins β (C/EBPβ), two adipogenic transcription factors, was also decreased by kaempferol and kaempferide treatment. In addition, western blot analysis also demonstrated that kaempferol and kaempferide reduced expression of heme oxygenase-1 (HO-1) and nuclear transcription factor-erythroid 2-related factor 2 (Nrf2). Molecular docking was performed to identify the direct molecular targets of kaempferol and kaempferide, and their binding to SCD-1, a critical regulator in lipid metabolism, was revealed. Taken together, our findings demonstrate that kaempferol and kaempferide could attenuate OA-induced lipid accumulation and oxidative stress in HepG2 cells, which might benefit the treatment of NAFLD.

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Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipogenesis and oxidative stress

Life Sciences ◽

10.1016/j.lfs.2016.06.001 ◽

2016 ◽

Vol 157 ◽

pp. 131-139 ◽

Cited By ~ 29

Author(s):

Caifeng Xie ◽

Zhen Chen ◽

Chengfu Zhang ◽

Xin Xu ◽

Jiangbo Jin ◽

...

Keyword(s):

Oxidative Stress ◽

Oleic Acid ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

And Oxidative Stress

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Plants from Ulleung island ameliorate lipid accumulation and oxidative stress in oleic acid-induced in HepG2 Cells

Korean Journal of Food Preservation ◽

10.11002/kjfp.2020.27.6.817 ◽

2020 ◽

Vol 27 (6) ◽

pp. 817-828

Author(s):

SukJin Kim ◽

Gun-Hee Kim

Keyword(s):

Oxidative Stress ◽

Oleic Acid ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

Ulleung Island ◽

And Oxidative Stress

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Mitochondrial-Targeting Antioxidant SS-31 Suppresses Airway Inflammation and Oxidative Stress Induced by Cigarette Smoke

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6644238 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

De-qing Yang ◽

Qiu-nan Zuo ◽

Tao Wang ◽

Dan Xu ◽

Liu Lian ◽

...

Keyword(s):

Oxidative Stress ◽

Western Blot ◽

Airway Inflammation ◽

Blot Analysis ◽

Western Blot Analysis ◽

Mapk Signaling ◽

Tnf Α ◽

And Oxidative Stress

This study investigated whether the mitochondrial-targeted peptide SS-31 can protect against cigarette smoke- (CS-) induced airway inflammation and oxidative stress in vitro and in vivo. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, and those in the experimental group were pretreated with SS-31 1 h before CS exposure. Pathologic changes and oxidative stress in lung tissue, inflammatory cell counts, and proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. The mechanistic basis for the effects of SS-31 on CS extract- (CSE-) induced airway inflammation and oxidative stress was investigated using BEAS-2B bronchial epithelial cells and by RNA sequencing and western blot analysis of lung tissues. SS-31 attenuated CS-induced inflammatory injury of the airway and reduced total cell, neutrophil, and macrophage counts and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, and matrix metalloproteinase (MMP) 9 levels in BALF. SS-31 also attenuated CS-induced oxidative stress by decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) activities and increasing that of superoxide dismutase (SOD). It also reversed CS-induced changes in the expression of mitochondrial fission protein (MFF) and optic atrophy (OPA) 1 and reduced the amount of cytochrome c released into the cytosol. Pretreatment with SS-31 normalized TNF-α, IL-6, and MMP9 expression, MDA and SOD activities, and ROS generation in CSE-treated BEAS-2B cells and reversed the changes in MFF and OPA1 expression. RNA sequencing and western blot analysis showed that SS-31 inhibited CS-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway in vitro and in vivo. Thus, SS-31 alleviates CS-induced airway inflammation and oxidative stress via modulation of mitochondrial function and regulation of MAPK signaling and thus has therapeutic potential for the treatment of airway disorders caused by smoking.

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Effect of high exposure of chlorogenic acid on lipid accumulation and oxidative stress in oleic acid-treated HepG2 cells

Chinese Herbal Medicines ◽

10.1016/j.chmed.2018.03.005 ◽

2018 ◽

Vol 10 (2) ◽

pp. 199-205 ◽

Cited By ~ 4

Author(s):

Ya-yun Liu ◽

Ting Zhai ◽

Qing-qing Yu ◽

Jing Zhu ◽

Yong Chen

Keyword(s):

Oxidative Stress ◽

Oleic Acid ◽

Chlorogenic Acid ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

High Exposure ◽

And Oxidative Stress

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Exogenous IGF-1 improves cognitive function in rats with high-fat diet consumption

Journal of Molecular Endocrinology ◽

10.1530/jme-19-0150 ◽

2020 ◽

Vol 64 (2) ◽

pp. 115-123 ◽

Cited By ~ 2

Author(s):

Feng Wang ◽

Lu Wang ◽

Yifeng Wang ◽

Dai Li ◽

Tianpeng Hu ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Function ◽

Western Blot ◽

Blot Analysis ◽

High Fat Diet ◽

Western Blot Analysis ◽

High Fat ◽

Anxiety Behavior ◽

And Oxidative Stress ◽

Creb Pathway

Insulin-like growth factor-1 (IGF-1) improves cognitive function, but its mechanism has not been elucidated. The aim of the study was to explore whether IGF-1 exerted its protective effect on cognitive function and anxiety behavior through the activation of PI3K/Akt/CREB pathway in high-fat diet rats. Neuronal cells HT22 were treated with nothing, IGF-1, IGF-1 + LY294002 or IGF-1 + 666-15. Expressions of p-PI3K, p-Akt and p-CREB were measured using Western blot analysis. Thirty C57BL/6J rats were used. After feeding with high-fat diet, normal saline, PEG-IGF-1, PEG-IGF-1 + LY294002 or PEG-IGF-1 + 666-15 was treated. Cognitive function and anxiety behavior were assessed by Morris water maze and open field test. Several inflammation and oxidative stress biomarkers were measured using recognized methods. Expressions of p-PI3K and p-CREB were also measured using Western blot analysis. After IGF-1 treatment in cells, expressions of p-PI3K, p-Akt and p-CREB were increased. Furthermore, LY294002 downregulated the expressions of these three proteins, but 666-15 only inhibited the expression of CREB in the cells. Compared with the control rats, we found abnormalities of cognitive function and anxiety behavior, inhibition of PI3K/Akt/CREB pathway and increase of oxidative stress and inflammation in high-fat diet rats. After PEG-IGF-1 treatment, the changes in high-fat diet rats were reversed. Then, we blocked the pathway and found that these blockers attenuated the protective effects of PEG-IGF-1. In conclusion, IGF-1 improved cognitive function and anxiety behavior in high-fat diet rats and inhibited inflammation and oxidative stress in hippocampus tissue through the activation of PI3K/Akt/CREB pathway.

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The Antitumor Effects of Britanin on Hepatocellular Carcinoma Cells and its Real-Time Evaluation by In Vivo Bioluminescence Imaging

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200227092623 ◽

2020 ◽

Vol 20 (9) ◽

pp. 1147-1156

Author(s):

Hanrui Li ◽

GeTao Du ◽

Lu Yang ◽

Liaojun Pang ◽

Yonghua Zhan

Keyword(s):

Hepatocellular Carcinoma ◽

Western Blot ◽

Blot Analysis ◽

Tumor Size ◽

Hepg2 Cells ◽

Western Blot Analysis ◽

Bioluminescence Imaging ◽

Antitumor Effects ◽

In Vivo Bioluminescence Imaging

Background: Hepatocellular carcinoma is cancer with many new cases and the highest mortality rate. Chemotherapy is the most commonly used method for the clinical treatment of hepatocellular carcinoma. Natural products have become clinically important chemotherapeutic drugs due to their great potential for pharmacological development. Many sesquiterpene lactone compounds have been proven to have antitumor effects on hepatocellular carcinoma. Objective: Britanin is a sesquiterpene lactone compound that can be considered for the treatment of hepatocellular carcinoma. The present study aimed to investigate the antitumor effect of britanin. Methods: BEL 7402 and HepG2 cells were used to study the cytotoxicity and antitumor effects of britanin. Preliminary studies on the nuclear factor kappa B pathway were conducted by western blot analysis. A BEL 7402-luc subcutaneous tumor model was established for the in vivo antitumor studies of britanin. In vivo bioluminescence imaging was conducted to monitor changes in tumor size. Results: The results of the cytotoxicity analysis showed that the IC50 values for britanin in BEL 7402 and HepG2 cells were 2.702μM and 6.006μM, respectively. The results of the colony formation demonstrated that the number of cells in a colony was reduced significantly after britanin treatment. And the results of transwell migration assays showed that the migration ability of tumor cells was significantly weakened after treatment with britanin. Tumor size measurements and staining results showed that tumor size was inhibited after britanin treatment. The western blot analysis results showed the inhibition of p65 protein expression and reduced the ratio of Bcl-2/Bax after treatment. Conclusion: A series of in vitro and in vivo experiments demonstrated that britanin had good antitumor effects and provided an option for hepatocellular carcinoma treatment.

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Is Oxidative Stress in Mice Brain Regions Diminished by 2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile?

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/194192 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

A. C. Fortes ◽

A. A. C. Almeida ◽

G. A. L. Oliveira ◽

P. S. Santos ◽

W. De Lucca Junior ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Western Blot ◽

Blot Analysis ◽

Western Blot Analysis ◽

Brain Regions ◽

Saline Control ◽

Control Group ◽

Nitrite Content

2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, 5TIO1, is a new 2-aminothiophene derivative with promising pharmacological activities. The aim of this study was to evaluate its antioxidant activity in different areas of mice central nervous system. Male Swiss adult mice were intraperitoneally treated with Tween 80 dissolved in 0.9% saline (control group) and 5TIO1 (0.1, 1, and 10 mg kg−1). Brain homogenates—hippocampus, striatum, frontal cortex, and cerebellum—were obtained after 24 h of observation. Superoxide dismutase and catalase activities, lipid peroxidation and nitrite content were measured using spectrophotometrical methods. To clarify the 5TIO1’s mechanism on oxidative stress, western blot analysis of superoxide dismutase and catalase was also performed. 5TIO1 decreased lipid peroxidation and nitrite content in all brain areas and increased the antioxidant enzymatic activities, specially, in cerebellum. The data of Western blot analysis did not demonstrate evidence of the upregulation of these enzymes after the administration of this compound. Our findings strongly support that 5TIO1 can protect the brain against neuronal damages regularly observed during neuropathologies.

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Curcumin Suppresses the Lipid Accumulation and Oxidative Stress Induced by Benzo[a]pyrene Toxicity in HepG2 Cells

Antioxidants ◽

10.3390/antiox10081314 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1314

Author(s):

Seung-Cheol Lee ◽

Seung-Cheol Jee ◽

Min Kim ◽

Soee Kim ◽

Min Kyoung Shin ◽

...

Keyword(s):

Oxidative Stress ◽

Cytochrome P450 ◽

Cell Viability ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

Nuclear Translocation ◽

The Body ◽

Ros Generation ◽

Related Factor ◽

And Oxidative Stress

Benzo[a]pyrene (B[a]P) is a potentially hepatotoxic group-1 carcinogen taken up by the body through ingestion of daily foods. B[a]P is widely known to cause DNA and protein damages, which are closely related to cell transformation. Accordingly, studies on natural bioactive compounds that attenuate such chemical-induced toxicities have significant impacts on public health. This study aimed to uncover the mechanism of curcumin, the major curcuminoid in turmeric (Curcuma longa), in modulating the lipid accumulation and oxidative stress mediated by B[a]P cytotoxicity in HepG2 cells. Curcumin treatment reduced the B[a]P-induced lipid accumulation and reactive oxygen spicies (ROS) upregulation and recovered the cell viability. Cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) and Cytochrome P450 subfamily B polypeptide 1 (CYP1B1) downregulation resulting from decreased aryl hydrocarbon receptor (AhR) translocation into nuclei attenuated the effects of B[a]P-induced lipid accumulation and repressed cell viability, respectively. Moreover, the curcumin-induced reduction in ROS generation decreased the nuclear translocation of Nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of phase-II detoxifying enzymes. These results indicate that curcumin suppresses B[a]P-induced lipid accumulation and ROS generation which can potentially induce nonalcoholic fatty liver disease (NAFLD) and can shed a light on the detoxifying effect of curcumin.

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Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/6021763 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Ruihong Wang ◽

Dawei Luo ◽

Zhiwei Li ◽

Huimin Han

Keyword(s):

Oxidative Stress ◽

Intervertebral Disc ◽

Western Blot ◽

Er Stress ◽

Nucleus Pulposus ◽

Blot Analysis ◽

Western Blot Analysis ◽

Dimethyl Fumarate ◽

Matrix Composition ◽

Type I

Background. Oxidative stress, inflammation, and nucleus pulposus cells (NPCs) apoptosis are involved in pathogenesis of intervertebral disc (IVD) degeneration (IVDD). Dimethyl fumarate (DMF) has been found to effectively depress oxidative stress and inflammation via the Nrf2 pathway. Hence, this project was designed to explore the underlying mechanisms of how DMF protects NPCs from damage by LPS challenge. Methods and Results. CCK8 assay and flow cytometry of apoptosis indicated that DMF treatment attenuated LPS-induced NPC damage. Western blot analysis demonstrated that DMF enhanced the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in LPS-challenged NPCs. DMF treatment significantly decreased the accumulation of ROS, downregulated inflammatory cytokines (p-NF-κB, IL-1β, and TNF-α), and ER stress-associated apoptosis proteins (Bip, calpain-1, caspase-12, caspase-3, and Bax) in LPS-challenged NPCs. The level of antiapoptotic protein Bcl-2 was promoted by DMF treatment in LPS-challenged NPCs. Glutathione (GSH) assay showed that DMF treatment improved reduced to oxidized glutathione ratio in LPS-challenged NPCs. Furthermore, the results of western blot analysis indicated that in LPS-challenged NPCs, DMF treatment ameliorated the elevated levels of matrix degradation enzymes (MMP-13, aggrecanase 1) and type I collagen and the reduced levels of matrix composition (type II collagen and ACAN). However, Nrf2 knockdown abolished these protective effects of DMF. Conclusion. Our data suggested that treatment with DMF mitigated LPS-induced oxidative stress, inflammation, and ER stress-associated apoptosis in NPCs via the Nrf2/HO-1 signaling pathway, thus reliving LPS-induced dysfunction of NPCs, which offered a novel potential pharmacological treatment strategy for IVDD.

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