Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP-1 in mice

Şahin, Erhan; Bağcı, Rıdvan; Aykanat, Nuriye Ezgi Bektur; Kaçar, Sedat; Şahıntürk, Varol

doi:10.1111/jfbc.13194

Cited by 31 publications

(17 citation statements)

References 29 publications

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“…, and it could improve lipid metabolism and antioxidative activity [73,74]. Silymarin is a lipophilic active complex extracted from milk thistle (Silybum marianum), and it contains several flavonolignans (like silybin, silydianin, silychristin, and isosilybin), among which, silybin had the most significant hepatoprotective effects [75,76]. Ginsenosides are amorphous compounds extracted from ginseng (Panax ginseng).…”

Section: Beneficial Bioactive Compounds From Coffee In Relationmentioning

confidence: 99%

Plant‐Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application

Gan

Shang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Fatty liver disease (FLD), including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), is a serious chronic metabolic disease that affects a wide range of people. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of FLD. The plant-based, high-fiber, and low-fat diet has been recommended to manage FLD for a long time. This review discusses the current state of the art into the effects, mechanisms, and clinical application of plant-based foods in NAFLD and AFLD, with highlighting related molecular mechanisms. Epidemiological evidence revealed that the consumption of several plant-based foods was beneficial to alleviating FLD. Further experimental studies found out that fruits, spices, teas, coffee, and other plants, as well as their bioactive compounds, such as resveratrol, anthocyanin, curcumin, and tea polyphenols, could alleviate FLD by ameliorating hepatic steatosis, oxidative stress, inflammation, gut dysbiosis, and apoptosis, as well as regulating autophagy and ethanol metabolism. More importantly, clinical trials confirmed the beneficial effects of plant-based foods on patients with fatty liver. However, several issues need to be further studied especially the safety and effective doses of plant-based foods and their bioactive compounds. Overall, certain plant-based foods are promising natural sources of bioactive compounds to prevent and alleviate fatty liver disease.

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Section: Beneficial Bioactive Compounds From Coffee In Relationmentioning

confidence: 99%

Plant‐Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application

Gan

Shang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…These treatments do not work specifically on the liver, and their effects are minimal compared to the side effects that accompany them [ 22 , 23 ]. The development of bio-active food material and medication, which can prevent and heal NAFLD and has few side effects, is required [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

Kim

Chang

Jeon

et al. 2020

IJMS

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A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

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“…Decreased expression of ER stress molecule GRP78 contributed to reducing fasting glucose and lipid pro le, and attenuating NAFLD [97][98][99].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking

Xing

Yang

et al. 2022

Preprint

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Background: Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disease with its incidence increasing annually. Shugan Xiaozhi (SGXZ) decoction, a composite traditional Chinese medicinal prescription, was demonstrated to exert a therapeutic effect on NAFLD. However, the underlying mechanisms were incompletely elucidated. In this study, the potential bioactive ingredients and mechanism of the SGXZ decoction against NAFLD were explored via network pharmacology and molecular docking. Methods: Compounds in SGXZ decoction were identified and collected from literature studies, and the corresponding targets were predicted through SEA database. Potential targets related to NAFLD were overlapped by using DisGeNET and GeneCards database. The compound-target-disease and PPI network were then constructed based on the putative intersection targets of SGXZ decoction and NAFLD to recognize the key compounds and targets. Functional enrichment analysis was performed to elucidate the biological process and signaling pathway that SGXZ decoction treated NAFLD. Finally, molecular docking combined with homology modeling was applied to further verify the binding between key active compounds and targets.Results: A total of 31 active compounds and 220 corresponding targets in SGXZ decoction were collected. Moreover, 1544 overlapped targets of NAFLD were obtained, of which 78 common targets were intersected with targets of SGXZ decoction. Key compounds and targets were recognized from compound-target-disease and PPI network. Functional enrichment analysis revealed that multiple biological pathways were annotated including insulin resistance, HIF-1, PI3K-Akt, and MAPK signaling pathways. Molecular docking confirmed that gallic acid, chlorogenic acid and isochlorogenic acid A could combine firmly with all of the key targets. Conclusion: SGXZ decoction could produce a promising effect for its multi-component, multi-target and multi-biological process in the treatment of NAFLD. The present study provides the novel insight into a comprehensive understanding for further study.

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Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP-1 in mice

Cited by 31 publications

References 29 publications

Plant‐Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application

Plant‐Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application

SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking

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