Protective effects of ginsenoside Rk3 against chronic alcohol-induced liver injury in mice through inhibition of inflammation, oxidative stress, and apoptosis

Liu, Qu; Zhu, Yanyan; Liu, Yannan; Yang, Haixia; Zhu, Chenhui; Ma, Ping; Deng, Jianjun; Fan, Daidi

doi:10.1016/j.fct.2019.02.032

Cited by 58 publications

(35 citation statements)

References 36 publications

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“…NF-kB-P65, as a key cytokine, plays a crucial role in inflammation and apoptosis. Qu et al [21] showed that the activation of NF-kB facilitated the release of anti-apoptotic factors in PC3 prostate carcinoma cells, reducing apoptosis. Also, Liu et al [22] showed that activation of AMPK increased NF-kB activity and reduced the expression of inflammatory cytokines by phosphorylating SIRT1 and FoxO3a.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway

et al. 2020

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Background: This study aimed to investigate the effects of dexmedetomidine in a rat model of sepsis-induced lung injury and the role of the adenosine monophosphate-activated protein kinase (AMPK) gene and silent information regulator 1 (SIRT1) gene signaling pathway. Material/Methods: Sixty 28-week-old healthy male Sprague-Dawley rats were randomly divided into three groups, the sham group, the model group, and the dexmedetomidine-treated group. The rat model of sepsis-induced lung injury was developed by surgical cecal ligation and puncture. Lung tissues examined histologically in the three study groups. Cell apoptosis was measured using the TUNEL assay, and the expression of inflammatory cytokines, tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), and IL-10 were measured in rat lung tissue by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated proteins and AMPK/SIRT1 pathway-associated protein expression levels were detected using Western blot. Results: Dexmedetomidine significantly increased the survival rate and reduced the body temperature of rats in the model group with sepsis-induced lung injury, reduced lung injury, significantly reduced apoptosis in lung tissues, and reduced the expression levels of TNF-a, and IL-1b, and increased the levels of IL-10. Dexmedetomidine significantly reduced the expression of caspase-3 in the rat lung tissue (P<0.01), and significantly increased the expression of Bcl-2/Bax and the phosphorylation levels of AMPK, SIRT1, nuclear factor-kB (NF-kB), and forkhead box class O 3a (FOXO3a). Conclusions: In a rat model of sepsis-induced lung injury, dexmedetomidine reduced lung damage by activating the AMPK/SIRT1 signaling pathway and reduced the expression of inflammatory cytokines and cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway

et al. 2020

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“…Apoptosis is a highly recognized feature of ALD [47]. Several studies have observed hepatocyte apoptosis in alcohol-induced liver injury [48,49]. An early study demonstrated that long-term vitamin D deficiency induced liver apoptosis [50].…”

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confidence: 99%

Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice

Chu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Vitamin D deficiency has been reported in alcoholics. This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice. Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury. In the VDD+EtOH group, mice were fed with modified diets, in which vitamin D was depleted. Vitamin D deficiency aggravated alcohol-induced liver injury. Furthermore, vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury. Although it has a little effect on hepatic TG content, vitamin D deficiency promoted alcohol-induced hepatic GSH depletion and lipid peroxidation. Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase (inos), two NADPH oxidase subunits p47phox and gp91phox, and heme oxygenase- (HO-) 1. By contrast, vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes, such as superoxide dismutase (sod) 1 and gshpx. In addition, vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines. Taken together, these results suggest that vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.

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“…For instance, Linoleic acid (CID5460332), a polyunsaturated omega-6 fatty acid, could significantly increase the protein levels of hepatic ALOX15 in Hepa-1c1c7 cells, which contributed to the pathogenesis of alcohol-induced liver injury (Zhang et al, 2017). Additionally, Linoleic acid has been reported to cause oxidative damage (Tong et al, 2016; Li et al, 2019; Qu et al, 2019; Zhang et al, 2019) and mediate selective loss of intrahepatic CD4(+) T lymphocytes, which leads to accelerated hepatocarcinogenesis (Ma et al, 2016). Several clinical case reports also indicate that linoleic acid may induce hepatic disease, such as acute hepatitis (Ramos et al, 2009; Rita and José, 2012; Mohammad et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

In silico Identification and Mechanism Exploration of Hepatotoxic Ingredients in Traditional Chinese Medicine

Cai

Guo

et al. 2019

Front. Pharmacol.

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Backgrounds and Aims Recently, a growing number of hepatotoxicity cases aroused by Traditional Chinese Medicine (TCM) have been reported, causing increasing concern. To date, the reported predictive models for drug induced liver injury show low prediction accuracy and there are still no related reports for hepatotoxicity evaluation of TCM systematically. Additionally, the mechanism of herb induced liver injury (HILI) still remains unknown. The aim of the study was to identify potential hepatotoxic ingredients in TCM and explore the molecular mechanism of TCM against HILI. Materials and Methods In this study, we developed consensus models for HILI prediction by integrating the best single classifiers. The consensus model with best performance was applied to identify the potential hepatotoxic ingredients from the Traditional Chinese Medicine Systems Pharmacology database (TCMSP). Systems pharmacology analyses, including multiple network construction and KEGG pathway enrichment, were performed to further explore the hepatotoxicity mechanism of TCM. Results 16 single classifiers were built by combining four machine learning methods with four different sets of fingerprints. After systematic evaluation, the best four single classifiers were selected, which achieved a Matthews correlation coefficient (MCC) value of 0.702, 0.691, 0.659, and 0.717, respectively. To improve the predictive capacity of single models, consensus prediction method was used to integrate the best four single classifiers. Results showed that the consensus model C-3 (MCC = 0.78) outperformed the four single classifiers and other consensus models. Subsequently, 5,666 potential hepatotoxic compounds were identified by C-3 model. We integrated the top 10 hepatotoxic herbs and discussed the hepatotoxicity mechanism of TCM via systems pharmacology approach. Finally, Chaihu was selected as the case study for exploring the molecular mechanism of hepatotoxicity. Conclusion Overall, this study provides a high accurate approach to predict HILI and an in silico perspective into understanding the hepatotoxicity mechanism of TCM, which might facilitate the discovery and development of new drugs.

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Protective effects of ginsenoside Rk3 against chronic alcohol-induced liver injury in mice through inhibition of inflammation, oxidative stress, and apoptosis

Cited by 58 publications

References 36 publications

The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway

The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway

Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice

In silico Identification and Mechanism Exploration of Hepatotoxic Ingredients in Traditional Chinese Medicine

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