Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract

Müller, Christian; Gardemann, Andreas; Keilhoff, Gerburg; Peter, Daniela; Wiswedel, Ingrid; Schild, Lorenz

doi:10.1016/j.phymed.2011.12.002

Cited by 41 publications

(29 citation statements)

References 45 publications

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“…The extract completely protected the cells from oxidative stress-induced apoptosis. Similar results have been obtained by Lin et al in their investigation using hepatocytes [7, 8]. …”

Section: Discussionsupporting

confidence: 91%

The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts

Lobo

Liu

2014

ISRN Dermatology

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Background. The objective of this paper is to demonstrate the effect of Gynostemma pentaphyllum extract on mouse dermal fibroblasts. Recent studies have shown that this plant may possess great antioxidant properties, which can be very beneficial in combating oxidative stress. Methods. Gynostemma pentaphyllum extract was prepared and mouse dermal fibroblasts were obtained and cultured as per our laboratory protocols. Twelve samples of cells were cultured under the same conditions and both negative and positive controls were established. Induction of oxidative stress was carried out using ultraviolet C (UVC) light. Viable cell count was carried out, using microscopy. The analysis of the overall results was processed using SPSS version 16.0. Results. Statistical analysis showed strong positive correlation between the concentration of Gynostemma pentaphyllum and the mean duration of cell viability (rs = 1), with a high level of statistical significance (P < 0.01). Likewise, strong positive correlation existed between trials of cell viability (rs = 0.988–1), with statistical significance (P < 0.01). Conclusion. Gynostemma pentaphyllum extract prolongs viability of mouse dermal fibroblasts damaged by UVC light-induced oxidative stress. The results show the potential benefits of this extract on dermal cell aging.

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“…The extract completely protected the cells from oxidative stress-induced apoptosis. Similar results have been obtained by Lin et al in their investigation using hepatocytes [7, 8]. …”

Section: Discussionsupporting

confidence: 91%

The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts

Lobo

Liu

2014

ISRN Dermatology

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“…Although the nature of NAFLD has been extensively studied, there is no effective therapy for disease clinically. The use of medicinal plants and their bioactive components continue to be evaluated as potential treatments for NAFLD . Seo et al .…”

Section: Discussionmentioning

confidence: 99%

“…The use of medicinal plants and their bioactive components continue to be evaluated as potential treatments for NAFLD. [5,22,23] Seo et al reported that Magnolia officinalis, a traditional oriental medicine used to treat liver diseases, attenuated the TG synthesis and lipid accumulation in NAFLD. [24] Wild ginseng has also been reported to prevent obesity in animal models by decreasing insulin resistance and body weight.…”

Section: Discussionmentioning

confidence: 99%

Wild ginseng cambial meristematic cells ameliorate hepatic steatosis and mitochondrial dysfunction in high-fat diet-fed mice

Lee

Cho

Jin³

et al. 2016

Journal of Pharmacy and Pharmacology

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“…Overall, lipotoxicity is most commonly induced by saturated fatty acids (SFAs), specifically palmitic acid (PA; 16:0), the most abundant SFA in the diet and in the circulation . The cellular mechanisms underlying SFA‐induced lipotoxicity in hepatocytes remain to be fully understood; however, it is well documented that endoplasmic reticulum stress and oxidative stress are the major intracellular pathways mechanistically involved in lipoapoptosis . Protecting hepatocytes from SFA‐induced hepatotoxicity provides a conceivable strategy for preventing the development of NAFLD.…”

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confidence: 99%

Sirtuin 3 acts as a negative regulator of autophagy dictating hepatocyte susceptibility to lipotoxicity

et al. 2017

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Lipotoxicity induced by saturated fatty acids (SFAs) plays a central role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be fully elucidated. SIRT3 is an NAD+-dependent deacetylase primarily located inside mitochondria. In this study, we demonstrated that a SFAs-rich high-fat diet (HFD) was more detrimental to the liver than an isocaloric unsaturated FAs-rich HFD. Unexpectedly, SIRT3 expression/activity were significantly elevated in the livers of mice exposed to the SFAs-rich HFD. Using cultured HepG2 and AML-12 hepatocytes, we demonstrated that unlike monounsaturated FAs, SFAs upregulates SIRT3 expression/activity. SIRT3 overexpression renders both the liver and hepatocytes susceptible to palmitate-induced cell death, which can be alleviated by SIRT3 siRNA transfection. In contrast, SIRT3 suppression protects hepatocytes from palmitate cytotoxicity. Further studies revealed that SIRT3 acts as a negative regulator of autophagy, whereby enhancing the susceptibility of hepatocytes to SFAs-induced cytotoxicity. Mechanistic investigations elucidate that SIRT3 overexpression causes manganese superoxide dismutase (MnSOD) deacetylation/activation, which depleted intracellular superoxide contents, leading to AMP-activated protein kinase (AMPK) inhibition and mTORC1 activation, resulting in autophagy suppression. In contrast, SIRT3 siRNA gene silencing enhances autophagy flux. The similar result was observed in the liver tissue from SIRT3 knockout mice. Conclusion our data identified SIRT3 to be a novel negative regulator of autophagy, whose activation by SFAs contributes to lipotoxicity in hepatocytes and suggest that restraining SIRT3 overactivation can be a potential therapeutic choice for the treatment of NAFLD as well as other metabolic disorders, with lipotoxicity being the principal pathomechanism.

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Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract

Cited by 41 publications

References 45 publications

The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts

The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts

Wild ginseng cambial meristematic cells ameliorate hepatic steatosis and mitochondrial dysfunction in high-fat diet-fed mice

Sirtuin 3 acts as a negative regulator of autophagy dictating hepatocyte susceptibility to lipotoxicity

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