Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder

Zhao, Xiaojuan; Yang, Yichen; Zheng, Yurong; Wang, Shan-Chun; Gu, Hongmei; Pan, Ying; Wang, Shui-Juan; Xu, Hongjiang; Kong, Ling-Dong

doi:10.1016/j.ejphar.2017.05.032

Cited by 53 publications

(37 citation statements)

References 23 publications

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“…Current studies have shown that consumption of fructose changes the lipid profile . Incir et al noticed an increase in serum triglyceride, TC, and LDL levels and a decrease in HDL levels in the fructose‐treated group.…”

Section: Discussionmentioning

confidence: 99%

“…Incir et al noticed an increase in serum triglyceride, TC, and LDL levels and a decrease in HDL levels in the fructose‐treated group. Zhao et al observed that administration of fructose with liquid, elevated triglyceride, TC, and LDL levels but nonsignificantly decreased the HDL levels. In our study, a significant increase in serum triglyceride and VLDL levels of the IR group was detected.…”

Section: Discussionmentioning

confidence: 99%

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Dipeptidyl peptidase‐4 inhibition prevents cell death via extrinsic and intrinsic apoptotic pathways in rat pancreas with insulin resistance

Nephan

Coşkun

Bolkent

2018

Cell Biochemistry & Function

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The study aims to evaluate the effect of saxagliptin, a specific inhibitor of dipeptidyl peptidase-4 enzymes, on body weight gain, lipid profiles, and cell death through apoptosis in rats with insulin resistance (IR). Male adult Sprague-Dawley rats (n = 32) were divided into 4 groups: control (Ctrl), IR, saxagliptin control, and IR treated with saxagliptin(IR + S). Insulin resistance was induced by 10% fructose in the drinking water for 8 weeks. Saxagliptin (10 mg/kg/day) was administrated by oral gavage for 2 weeks. Biochemical parameters were measured spectrophotometrically. Peptides were determined by the streptavidin-biotin-peroxidase method. Although the amount of food and liquid consumed are inversely proportional, the calories received are almost equal between both Ctrl and IR groups, as well as IR and IR + S groups. Increased homeostasis model assessment for insulin resistance, HOMA-β, triglycerides, and very low-density lipoprotein in the IR group were comparatively decreased by saxagliptin administration. The area percentage of caspase-3 and apoptotic peptidase activating factor-1 immunopositive cells in the IR + S group decreased compared with the IR group. Similarly, the percentages of caspase-8 and -9 immunopositive cells in the IR group were higher than the IR + S group. It was observed that the percentage of poly (ADP-ribose) polymerase-1 immunopositive cells was increased in the IR + S group compared with the IR group. Thus, saxagliptin may prevent IR-induced apoptotic cell death and regulate impaired homeostasis model assessment for insulin resistance and serum lipid levels.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase‐4 inhibition prevents cell death via extrinsic and intrinsic apoptotic pathways in rat pancreas with insulin resistance

Nephan

Coşkun

Bolkent

2018

Cell Biochemistry & Function

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“…In response to pathogenic stimuli such as endotoxin, steatosis sensitizes the liver to induce hydrogen peroxide, superoxide, and multiple proinflammatory cytokines (IL-6, TNF-α, etc. ), which further resulting in inflammasome and NF-κB signaling activation [3,4]. Therefore, pharmacological approaches to switch off the inflammatory response before irreversible damage might be pivotal therapeutic intervention strategies for NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Exogenous Hydrogen Sulfide Alleviates-Induced Intracellular Inflammation in HepG2 Cells

Wang

et al. 2019

Exp Clin Endocrinol Diabetes

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Fatty acids induced hepatic inflammation plays an important role in nonalcoholic fatty liver disease (NAFLD) pathogenesis. Hydrogen sulfide (H2S), an endogenous gasotransmitter, has been established to possess potent anti-inflammation in various human organs. However, the anti-inflammation property of H2S in the fatty liver is still needed to further elucidate. Hence, this study aimed to investigate whether exogenous H2S can protect hepatocytes against inﬂammation induced by palmitic acid (PA). HepG2 hepatocytes were exposed to PA for 24 h to induce free fatty acids-induced inflammation. The cells were pretreated with NaHS (a donor of H2S) before exposure to PA. Cell viability, inflammatory cytokines (TNF-α, IL-6 and IL-1β), NLRP3 inflammasome and NF-κB were measured by a combination of MTT assay, ELISA, Western blot and Immunofluorescence. Here, we found that exogenous H2S dose-dependently inhibited the expression of pro-inflammatory cytokines, NLRP3 inflammasome and activation of NF-κB signaling in PA-induced HepG2 cells. Thus, H2S might be a candidate therapeutic agent against NAFLD.

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“…Recently, MgIG has also been shown to exert its hepatoprotective effect against compounds such as cyclophosphamide ( Jiang et al, 2017 ) and doxorubicin ( Wu et al, 2018 ) by increasing the activity of anti-oxidant enzymes and reducing the inflammatory response. Mechanistically, studies have shown that the anti-inflammatory activity of MgIG is attributed to its potential to inhibit inflammatory-associated pathways such as STAT3 ( Tang et al, 2015 ), phospholipase A 2 /arachidonic ( Xie et al, 2015 ) and NF-κB pathways ( Jiang et al, 2017 ; Zhao et al, 2017 ). Taken together, these studies have illustrated the hepatoprotective effects of MgIG in various liver injuries.…”

Section: Introductionmentioning

confidence: 99%

Magnesium Isoglycyrrhizinate Ameliorates Fibrosis and Disrupts TGF-β-Mediated SMAD Pathway in Activated Hepatic Stellate Cell Line LX2

et al. 2018

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Liver fibrosis is a histological change often attributed to the activation of hepatic stellate cells (HSCs) and the excessive formation of scar tissues in the liver. Advanced stages of the disease frequently lead to cirrhosis. Magnesium isoglycyrrhizinate (MgIG) has been accepted as a hepatoprotective drug with the potential of alleviating inflammatory conditions and thus promote liver recovery from viral- or drug-induced injury. While MgIG has been empirically integrated into the clinics to treat some liver diseases, its anti-fibrotic effect and the associated mechanisms remain poorly characterized. Herein, we demonstrated that 1 mg/ml MgIG attenuated the production of αSMA and collagen-1 in activated HSCs using TGF-β1-induced human HSCs LX2 as the fibrotic cell model. We found that MgIG exerts an inhibitory effect on the TGF-β-SMAD signaling pathway by arresting the binding of downstream transcription factors SMAD2/3 and SMAD4. Furthermore, MgIG was shown to suppress proliferation and induce senescence of activated LX2 cells. Protein expression of p27 and enzymatic activity of senescence-associated β-galactosidase were elevated upon exposure to MgIG. In addition, we observed that exposure of activated LX2 cells to MgIG reduces TGF-β-induced apoptosis. Interestingly, a lower toxicity profile was observed when human fetal hepatocytes LO2 were exposed to the same concentration and duration of the drug, suggesting the specificity of MgIG effect toward activated HSCs. Overall, hepatoprotective concentrations of MgIG is shown to exert a direct effect on liver fibrosis through inhibiting TGF-β-signaling, in which SMAD2/3 pathway could be one of the mechanisms responsible for the fibrotic response, thereby restoring the surviving cells toward a more quiescent phenotype. This provides critical mechanistic insights to support an otherwise empirical therapy.

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Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder

Cited by 53 publications

References 23 publications

Dipeptidyl peptidase‐4 inhibition prevents cell death via extrinsic and intrinsic apoptotic pathways in rat pancreas with insulin resistance

Dipeptidyl peptidase‐4 inhibition prevents cell death via extrinsic and intrinsic apoptotic pathways in rat pancreas with insulin resistance

Exogenous Hydrogen Sulfide Alleviates-Induced Intracellular Inflammation in HepG2 Cells

Magnesium Isoglycyrrhizinate Ameliorates Fibrosis and Disrupts TGF-β-Mediated SMAD Pathway in Activated Hepatic Stellate Cell Line LX2

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