Limits...
Ruscogenin ameliorates experimental nonalcoholic steatohepatitis via suppressing lipogenesis and inflammatory pathway.

Lu HJ, Tzeng TF, Liou SS, Chang CJ, Yang C, Wu MC, Liu IM - Biomed Res Int (2014)

Bottom Line: Ruscogenin (10.0 μmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells.Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis.Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins in β-oxidation pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Neipu Township, Pingtung County, Taiwan.

ABSTRACT
The aim of the study was to investigate the protective effects of ruscogenin, a major steroid sapogenin in Ophiopogon japonicus, on experimental models of nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 μmol/l palmitic acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h. Ruscogenin (10.0 μmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis. Gene expression of inflammatory cytokines, chemoattractive mediator, nuclear transcription factor-(NF-) κB, and α-smooth muscle actin were increased in the HFD group, which were attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins in β-oxidation pathway.

Show MeSH

Related in: MedlinePlus

Effects of ruscogenin (RUS) on PA-induced lipids accumulation and inflammatory cytokines overproduction in HepG2 cells. Cells were exposed to PA (300 μmol/L) for 24 h with or without the preincubation of 0.1 (RUS 0.1), 1.0 (RUS 1.0), or 10.0 μmol/L ruscogenin (RUS 10.0). (a) Representative Oil Red O staining of cells with different treatments is shown. Cells were examined by light microscopy at a magnification of 400x. (b) Intracellular TG content was measured by an ELISA assay. TG concentration was normalized by protein content. (c) Inflammatory cytokines in cell-free culture supernatants were determined by ELISA kits. The results are presented as the mean ± SEM of four experiments. aP < 0.05 and bP < 0.01 compared to the control values of untreated cells (control), respectively. cP < 0.05 and dP < 0.01 compared to the values of PA-treated cells (PA), respectively.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4127260&req=5

fig2: Effects of ruscogenin (RUS) on PA-induced lipids accumulation and inflammatory cytokines overproduction in HepG2 cells. Cells were exposed to PA (300 μmol/L) for 24 h with or without the preincubation of 0.1 (RUS 0.1), 1.0 (RUS 1.0), or 10.0 μmol/L ruscogenin (RUS 10.0). (a) Representative Oil Red O staining of cells with different treatments is shown. Cells were examined by light microscopy at a magnification of 400x. (b) Intracellular TG content was measured by an ELISA assay. TG concentration was normalized by protein content. (c) Inflammatory cytokines in cell-free culture supernatants were determined by ELISA kits. The results are presented as the mean ± SEM of four experiments. aP < 0.05 and bP < 0.01 compared to the control values of untreated cells (control), respectively. cP < 0.05 and dP < 0.01 compared to the values of PA-treated cells (PA), respectively.

Mentions: The lipid accumulation was measured by Oil Red O staining. As shown in Figure 2(a), HepG2 cells treated for 24 h with PA exhibited significant lipid droplet accumulation compared with untreated cells. Preincubation with ruscogenin significantly prevented PA-induced lipid deposition and the most effective inhibition of lipid accumulation occurred at a dose of 10 μmol/L (Figure 2(a)). Consistently, treatment with PA resulted in an obvious increase in TG content compared with untreated cells, which was attenuated significantly by pretreatment with ruscogenin at a concentration of 10 μmol/L (Figure 2(b)). Ruscogenin alone or vehicle did not affect basal levels of lipid deposition (data not shown).


Ruscogenin ameliorates experimental nonalcoholic steatohepatitis via suppressing lipogenesis and inflammatory pathway.

Lu HJ, Tzeng TF, Liou SS, Chang CJ, Yang C, Wu MC, Liu IM - Biomed Res Int (2014)

Effects of ruscogenin (RUS) on PA-induced lipids accumulation and inflammatory cytokines overproduction in HepG2 cells. Cells were exposed to PA (300 μmol/L) for 24 h with or without the preincubation of 0.1 (RUS 0.1), 1.0 (RUS 1.0), or 10.0 μmol/L ruscogenin (RUS 10.0). (a) Representative Oil Red O staining of cells with different treatments is shown. Cells were examined by light microscopy at a magnification of 400x. (b) Intracellular TG content was measured by an ELISA assay. TG concentration was normalized by protein content. (c) Inflammatory cytokines in cell-free culture supernatants were determined by ELISA kits. The results are presented as the mean ± SEM of four experiments. aP < 0.05 and bP < 0.01 compared to the control values of untreated cells (control), respectively. cP < 0.05 and dP < 0.01 compared to the values of PA-treated cells (PA), respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127260&req=5

fig2: Effects of ruscogenin (RUS) on PA-induced lipids accumulation and inflammatory cytokines overproduction in HepG2 cells. Cells were exposed to PA (300 μmol/L) for 24 h with or without the preincubation of 0.1 (RUS 0.1), 1.0 (RUS 1.0), or 10.0 μmol/L ruscogenin (RUS 10.0). (a) Representative Oil Red O staining of cells with different treatments is shown. Cells were examined by light microscopy at a magnification of 400x. (b) Intracellular TG content was measured by an ELISA assay. TG concentration was normalized by protein content. (c) Inflammatory cytokines in cell-free culture supernatants were determined by ELISA kits. The results are presented as the mean ± SEM of four experiments. aP < 0.05 and bP < 0.01 compared to the control values of untreated cells (control), respectively. cP < 0.05 and dP < 0.01 compared to the values of PA-treated cells (PA), respectively.
Mentions: The lipid accumulation was measured by Oil Red O staining. As shown in Figure 2(a), HepG2 cells treated for 24 h with PA exhibited significant lipid droplet accumulation compared with untreated cells. Preincubation with ruscogenin significantly prevented PA-induced lipid deposition and the most effective inhibition of lipid accumulation occurred at a dose of 10 μmol/L (Figure 2(a)). Consistently, treatment with PA resulted in an obvious increase in TG content compared with untreated cells, which was attenuated significantly by pretreatment with ruscogenin at a concentration of 10 μmol/L (Figure 2(b)). Ruscogenin alone or vehicle did not affect basal levels of lipid deposition (data not shown).

Bottom Line: Ruscogenin (10.0 μmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells.Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis.Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins in β-oxidation pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Neipu Township, Pingtung County, Taiwan.

ABSTRACT
The aim of the study was to investigate the protective effects of ruscogenin, a major steroid sapogenin in Ophiopogon japonicus, on experimental models of nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 μmol/l palmitic acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h. Ruscogenin (10.0 μmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis. Gene expression of inflammatory cytokines, chemoattractive mediator, nuclear transcription factor-(NF-) κB, and α-smooth muscle actin were increased in the HFD group, which were attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins in β-oxidation pathway.

Show MeSH
Related in: MedlinePlus