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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.

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Related in: MedlinePlus

Representative images of F4/80 staining in livers from RCD- or HFD-fed hamsters receiving 8 weeks of treatments. Photomicrographs are of tissues isolated from vehicle-treated RCD-fed hamsters (RCD-vehicle), vehicle-treated HFD-fed hamsters (HFD-vehicle), or ruscogenin (3.0 mg/kg/day) treated HFD-fed hamsters (HFD-ruscogenin). Arrows indicate inflammatory foci. Quantification of hepatic macrophage accumulation is presented as the percentage of the brown stained area relative to the whole area of the photomicrograph (original magnification, 400x). Values (mean ± SEM) were obtained from 5 animals in each group. bP < 0.01 compared to vehicle-treated RCD-fed hamsters. cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters in each group, respectively.
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fig4: Representative images of F4/80 staining in livers from RCD- or HFD-fed hamsters receiving 8 weeks of treatments. Photomicrographs are of tissues isolated from vehicle-treated RCD-fed hamsters (RCD-vehicle), vehicle-treated HFD-fed hamsters (HFD-vehicle), or ruscogenin (3.0 mg/kg/day) treated HFD-fed hamsters (HFD-ruscogenin). Arrows indicate inflammatory foci. Quantification of hepatic macrophage accumulation is presented as the percentage of the brown stained area relative to the whole area of the photomicrograph (original magnification, 400x). Values (mean ± SEM) were obtained from 5 animals in each group. bP < 0.01 compared to vehicle-treated RCD-fed hamsters. cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters in each group, respectively.

Mentions: Livers from RCD-fed hamsters did not show any significant macrophage (F4/80-positive cells) infiltration (Figure 4). In contrast, HFD-fed hamsters demonstrated prominent macrophage infiltration of the liver (Figure 4). Treatment of HFD-fed hamsters with ruscogenin (3.0 mg/kg/day) for 8 weeks showed a marked reduction in macrophage influx by 29.3%, when compared with their vehicle-treated counterparts (Figure 4).


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)

Representative images of F4/80 staining in livers from RCD- or HFD-fed hamsters receiving 8 weeks of treatments. Photomicrographs are of tissues isolated from vehicle-treated RCD-fed hamsters (RCD-vehicle), vehicle-treated HFD-fed hamsters (HFD-vehicle), or ruscogenin (3.0 mg/kg/day) treated HFD-fed hamsters (HFD-ruscogenin). Arrows indicate inflammatory foci. Quantification of hepatic macrophage accumulation is presented as the percentage of the brown stained area relative to the whole area of the photomicrograph (original magnification, 400x). Values (mean ± SEM) were obtained from 5 animals in each group. bP < 0.01 compared to vehicle-treated RCD-fed hamsters. cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters in each group, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Representative images of F4/80 staining in livers from RCD- or HFD-fed hamsters receiving 8 weeks of treatments. Photomicrographs are of tissues isolated from vehicle-treated RCD-fed hamsters (RCD-vehicle), vehicle-treated HFD-fed hamsters (HFD-vehicle), or ruscogenin (3.0 mg/kg/day) treated HFD-fed hamsters (HFD-ruscogenin). Arrows indicate inflammatory foci. Quantification of hepatic macrophage accumulation is presented as the percentage of the brown stained area relative to the whole area of the photomicrograph (original magnification, 400x). Values (mean ± SEM) were obtained from 5 animals in each group. bP < 0.01 compared to vehicle-treated RCD-fed hamsters. cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters in each group, respectively.
Mentions: Livers from RCD-fed hamsters did not show any significant macrophage (F4/80-positive cells) infiltration (Figure 4). In contrast, HFD-fed hamsters demonstrated prominent macrophage infiltration of the liver (Figure 4). Treatment of HFD-fed hamsters with ruscogenin (3.0 mg/kg/day) for 8 weeks showed a marked reduction in macrophage influx by 29.3%, when compared with their vehicle-treated counterparts (Figure 4).

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