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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.


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(A,B) The effect of nuciferine or siRNA PASK on lipogenic genes related to hepatic steatosis in HepG2 cells. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 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 < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. (Control, siRNA scrambled; NF, Nuciferine.)
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Figure 5: (A,B) The effect of nuciferine or siRNA PASK on lipogenic genes related to hepatic steatosis in HepG2 cells. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 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 < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. (Control, siRNA scrambled; NF, Nuciferine.)

Mentions: To decipher the possible mechanism underlying the nuciferine-mediated effect on lipogenesis, nine important genes involved in lipogenesis were evaluated. According to results of the mRNA expression by RT-qPCR, the expression of PASK, SREBP-1c, fatty acid synthase (FAS), acetyl-CoA (ACC), stearoyl-CoA desaturase 1 1 (SCD1), PPAR-α and PPAR-γ was increased in OA-treated cells compared with the control (∗P < 0.05 and ∗∗∗P < 0.001), and this increase could be significantly reversed by nuciferine (10, 25, and 50 μM) and siRNA PASK. Meanwhile, the level of AMPK and protein kinase B (Akt) showed significantly decreased in OA-induced HepG2 cells (∗∗P < 0.01 and ∗∗∗P < 0.001), and they both increased when treated with nuciferine and siRNA PASK (∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. OA) (Figures 5A,B). These findings demonstrate that nuciferine could attenuate lipid accumulation by regulating the expression of relevant target genes involved in lipogenesis, which was accompanied with downregulated expression of PASK and was consistent with alterations of relevant genes in siRNA PASK group.


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)

(A,B) The effect of nuciferine or siRNA PASK on lipogenic genes related to hepatic steatosis in HepG2 cells. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 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 < 0.05, ∗∗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 5: (A,B) The effect of nuciferine or siRNA PASK on lipogenic genes related to hepatic steatosis in HepG2 cells. SiRNA PASK HepG2 cells and HepG2 cells incubated with increased concentrations of nuciferine (NF: 10, 25, and 50 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 < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. (Control, siRNA scrambled; NF, Nuciferine.)
Mentions: To decipher the possible mechanism underlying the nuciferine-mediated effect on lipogenesis, nine important genes involved in lipogenesis were evaluated. According to results of the mRNA expression by RT-qPCR, the expression of PASK, SREBP-1c, fatty acid synthase (FAS), acetyl-CoA (ACC), stearoyl-CoA desaturase 1 1 (SCD1), PPAR-α and PPAR-γ was increased in OA-treated cells compared with the control (∗P < 0.05 and ∗∗∗P < 0.001), and this increase could be significantly reversed by nuciferine (10, 25, and 50 μM) and siRNA PASK. Meanwhile, the level of AMPK and protein kinase B (Akt) showed significantly decreased in OA-induced HepG2 cells (∗∗P < 0.01 and ∗∗∗P < 0.001), and they both increased when treated with nuciferine and siRNA PASK (∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. OA) (Figures 5A,B). These findings demonstrate that nuciferine could attenuate lipid accumulation by regulating the expression of relevant target genes involved in lipogenesis, which was accompanied with downregulated expression of PASK and was consistent with alterations of relevant genes in siRNA PASK group.

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