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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

Real-time PCR analysis of mRNA expression of NF-κB-dependent proinflammatory markers in the livers of HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day). The mRNA expressions of the inflammatory cytokines and NF-κB were normalized to an internal control (β-actin). Animals not receiving any treatment were given the same volume of vehicle used to dissolve ruscogenin. Similar results were obtained with an additional 4 replications. Data were expressed as the mean with SEM (n = 5 per group) in each column. aP < 0.01 and 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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fig5: Real-time PCR analysis of mRNA expression of NF-κB-dependent proinflammatory markers in the livers of HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day). The mRNA expressions of the inflammatory cytokines and NF-κB were normalized to an internal control (β-actin). Animals not receiving any treatment were given the same volume of vehicle used to dissolve ruscogenin. Similar results were obtained with an additional 4 replications. Data were expressed as the mean with SEM (n = 5 per group) in each column. aP < 0.01 and 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: All inflammatory mediators were expressed at very low levels in the livers of RCD-fed hamsters (Figure 5). In HFD-fed hamsters, hepatic mRNA levels of MCP-1, TNF-α, IL-1β, IL-6, and NF-κB were significantly increased compared to RCD-fed group (Figure 5). These increases were approached to control values in hamsters treated with ruscogenin. In addition, the hepatic fibrosis index of α-SMA in HFD-fed hamsters was significantly increased to 4.3-fold of that observed in the RCD-fed group and decreased (41.5% decreases) by ruscogenin treatment (Figure 5).


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)

Real-time PCR analysis of mRNA expression of NF-κB-dependent proinflammatory markers in the livers of HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day). The mRNA expressions of the inflammatory cytokines and NF-κB were normalized to an internal control (β-actin). Animals not receiving any treatment were given the same volume of vehicle used to dissolve ruscogenin. Similar results were obtained with an additional 4 replications. Data were expressed as the mean with SEM (n = 5 per group) in each column. aP < 0.01 and 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

fig5: Real-time PCR analysis of mRNA expression of NF-κB-dependent proinflammatory markers in the livers of HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day). The mRNA expressions of the inflammatory cytokines and NF-κB were normalized to an internal control (β-actin). Animals not receiving any treatment were given the same volume of vehicle used to dissolve ruscogenin. Similar results were obtained with an additional 4 replications. Data were expressed as the mean with SEM (n = 5 per group) in each column. aP < 0.01 and 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: All inflammatory mediators were expressed at very low levels in the livers of RCD-fed hamsters (Figure 5). In HFD-fed hamsters, hepatic mRNA levels of MCP-1, TNF-α, IL-1β, IL-6, and NF-κB were significantly increased compared to RCD-fed group (Figure 5). These increases were approached to control values in hamsters treated with ruscogenin. In addition, the hepatic fibrosis index of α-SMA in HFD-fed hamsters was significantly increased to 4.3-fold of that observed in the RCD-fed group and decreased (41.5% decreases) by ruscogenin treatment (Figure 5).

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