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Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells.

Zhang DD, Zhang JG, Wu X, Liu Y, Gu SY, Zhu GH, Wang YZ, Liu GL, Li XY - Front Pharmacol (2015)

Bottom Line: It was found that nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG) accumulation and was effective in decreasing fatty acid (FFAs).Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK.In addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK group.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine Shanghai, China.

ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated with lipotoxicity, lipid peroxidation, oxidative stress, and inflammation. Nuciferine, an active ingredient extracted from the natural lotus leaf, has been reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, and gene expression. The aim of the present study was to investigate the protective effect of nuciferine against NAFLD and its inhibitory effect on PASK, exploring the possible underlying mechanism of nuciferine-mediated inhibition on NAFLD. Relevant biochemical parameters (lipid accumulation, extent of oxidative stress and release of inflammation cytokines) in oleic acid (OA)-induced HepG2 cells that mimicked steatosis in vitro were measured and compared with the control. It was found that nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG) accumulation and was effective in decreasing fatty acid (FFAs). The content of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were increased respectively by nuciferine and siRNA PASK without increase in glutathione (GSH). Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK. In addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK group. IL-10 was increased by nuciferine and siRNA PASK respectively. Further investigation revealed that nuciferine and siRNA PASK could respectively regulate the expression of target genes involved in lipogenesis and inflammation, suggesting that nuciferine may be a potential therapeutic treatment for NAFLD. Furthermore, the modulated effect of nuciferine on (OA)-induced HepG2 cells lipogenesis and inflammation, which was accompanied with PASK inhibition, was also consistent with siRNA PASK, implying that PASK might play a role in nuciferine-mediated regulation on NAFLD.

No MeSH data available.


Related in: MedlinePlus

The effect of nuciferine or siRNA PASK on cell lipotoxicity in HepG2 cells of OA-induced hepatic steatosis. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 μM) or vitamin E (25 μM) both treated with OA (40 μM). The measurement was described in the Section “Materials and Methods”. Values are Mean ± SEM of three independent experiments performed in triplicates. Significant differences with OA group were designated as ∗∗P < 0.01 and ∗∗∗P < 0.001. (Control, siRNA scrambled; NF, Nuciferine.)
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Figure 4: The effect of nuciferine or siRNA PASK on cell lipotoxicity in HepG2 cells of OA-induced hepatic steatosis. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 μM) or vitamin E (25 μM) both treated with OA (40 μM). The measurement was described in the Section “Materials and Methods”. Values are Mean ± SEM of three independent experiments performed in triplicates. Significant differences with OA group were designated as ∗∗P < 0.01 and ∗∗∗P < 0.001. (Control, siRNA scrambled; NF, Nuciferine.)

Mentions: To further explore the regulatory effect of nuciferine on lipid accumulation, the lipotoxicity caused by a cluster of FFAs that induced hepatic steatosis was measured. The addition of OA resulted in a 2.57-fold increase in FFAs as compared with the control (∗∗∗P < 0.001). The increased concentration of nuciferine decreased the FFAs level by 18.66, 39 and 44.01% respectively (∗∗P < 0.01 vs. OA), while vitamin E (25 μM) and siRNA PASK inhibited cellular FFAs by 42.81% (∗∗P < 0.01 vs. OA) and 50.22% (∗∗∗P < 0.001 vs. OA) respectively as compared with OA group (Figure 4). These data indicate that nuciferine and siRNA PASK played a regulatory role in attenuating lipid accumulation, similarly.


Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells.

Zhang DD, Zhang JG, Wu X, Liu Y, Gu SY, Zhu GH, Wang YZ, Liu GL, Li XY - Front Pharmacol (2015)

The effect of nuciferine or siRNA PASK on cell lipotoxicity in HepG2 cells of OA-induced hepatic steatosis. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 μM) or vitamin E (25 μM) both treated with OA (40 μM). The measurement was described in the Section “Materials and Methods”. Values are Mean ± SEM of three independent experiments performed in triplicates. Significant differences with OA group were designated as ∗∗P < 0.01 and ∗∗∗P < 0.001. (Control, siRNA scrambled; NF, Nuciferine.)
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 4: The effect of nuciferine or siRNA PASK on cell lipotoxicity in HepG2 cells of OA-induced hepatic steatosis. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 μM) or vitamin E (25 μM) both treated with OA (40 μM). The measurement was described in the Section “Materials and Methods”. Values are Mean ± SEM of three independent experiments performed in triplicates. Significant differences with OA group were designated as ∗∗P < 0.01 and ∗∗∗P < 0.001. (Control, siRNA scrambled; NF, Nuciferine.)
Mentions: To further explore the regulatory effect of nuciferine on lipid accumulation, the lipotoxicity caused by a cluster of FFAs that induced hepatic steatosis was measured. The addition of OA resulted in a 2.57-fold increase in FFAs as compared with the control (∗∗∗P < 0.001). The increased concentration of nuciferine decreased the FFAs level by 18.66, 39 and 44.01% respectively (∗∗P < 0.01 vs. OA), while vitamin E (25 μM) and siRNA PASK inhibited cellular FFAs by 42.81% (∗∗P < 0.01 vs. OA) and 50.22% (∗∗∗P < 0.001 vs. OA) respectively as compared with OA group (Figure 4). These data indicate that nuciferine and siRNA PASK played a regulatory role in attenuating lipid accumulation, similarly.

Bottom Line: It was found that nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG) accumulation and was effective in decreasing fatty acid (FFAs).Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK.In addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK group.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine Shanghai, China.

ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated with lipotoxicity, lipid peroxidation, oxidative stress, and inflammation. Nuciferine, an active ingredient extracted from the natural lotus leaf, has been reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, and gene expression. The aim of the present study was to investigate the protective effect of nuciferine against NAFLD and its inhibitory effect on PASK, exploring the possible underlying mechanism of nuciferine-mediated inhibition on NAFLD. Relevant biochemical parameters (lipid accumulation, extent of oxidative stress and release of inflammation cytokines) in oleic acid (OA)-induced HepG2 cells that mimicked steatosis in vitro were measured and compared with the control. It was found that nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG) accumulation and was effective in decreasing fatty acid (FFAs). The content of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were increased respectively by nuciferine and siRNA PASK without increase in glutathione (GSH). Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK. In addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK group. IL-10 was increased by nuciferine and siRNA PASK respectively. Further investigation revealed that nuciferine and siRNA PASK could respectively regulate the expression of target genes involved in lipogenesis and inflammation, suggesting that nuciferine may be a potential therapeutic treatment for NAFLD. Furthermore, the modulated effect of nuciferine on (OA)-induced HepG2 cells lipogenesis and inflammation, which was accompanied with PASK inhibition, was also consistent with siRNA PASK, implying that PASK might play a role in nuciferine-mediated regulation on NAFLD.

No MeSH data available.


Related in: MedlinePlus