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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

The hepatic mRNA levels of β-oxidation-related genes (a) and lipogenic genes (b) in HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day; HFD-RUS). The mRNA expressions of the β-oxidation-related genes and lipogenic genes were measured by RT-PCR and 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. bP < 0.01 compared to vehicle-treated RCD-fed hamsters (RCD-vehicle). cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters (HFD-vehicle) in each group, respectively.
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fig6: The hepatic mRNA levels of β-oxidation-related genes (a) and lipogenic genes (b) in HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day; HFD-RUS). The mRNA expressions of the β-oxidation-related genes and lipogenic genes were measured by RT-PCR and 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. bP < 0.01 compared to vehicle-treated RCD-fed hamsters (RCD-vehicle). cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters (HFD-vehicle) in each group, respectively.

Mentions: The mRNA levels of PPARα in livers of HFD-fed hamsters were decreased to 38.2% of those of the RCD-fed group (Figure 6(a)). Administration of ruscogenin to HFD-fed hamsters for 8 weeks significantly upregulated hepatic PPARα mRNA levels to 1.7-fold that of vehicle-treated counterparts (Figure 6(a)). Hepatic mRNA levels of PGC-1α, CPT-1, UCP2, and UCP3 in HFD-fed hamsters were clearly lower than those of the RCD-fed group and were upregulated by ruscogenin treatment (173.2, 144.3, 163.2, and 198.3% increases, resp.) (Figure 6(a)).


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)

The hepatic mRNA levels of β-oxidation-related genes (a) and lipogenic genes (b) in HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day; HFD-RUS). The mRNA expressions of the β-oxidation-related genes and lipogenic genes were measured by RT-PCR and 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. bP < 0.01 compared to vehicle-treated RCD-fed hamsters (RCD-vehicle). cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters (HFD-vehicle) in each group, respectively.
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Related In: Results  -  Collection

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fig6: The hepatic mRNA levels of β-oxidation-related genes (a) and lipogenic genes (b) in HFD-fed hamsters receiving 8 weeks of treatment with ruscogenin (3.0 mg/kg/day; HFD-RUS). The mRNA expressions of the β-oxidation-related genes and lipogenic genes were measured by RT-PCR and 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. bP < 0.01 compared to vehicle-treated RCD-fed hamsters (RCD-vehicle). cP < 0.05 and dP < 0.01 compared to the values of vehicle-treated HFD-fed hamsters (HFD-vehicle) in each group, respectively.
Mentions: The mRNA levels of PPARα in livers of HFD-fed hamsters were decreased to 38.2% of those of the RCD-fed group (Figure 6(a)). Administration of ruscogenin to HFD-fed hamsters for 8 weeks significantly upregulated hepatic PPARα mRNA levels to 1.7-fold that of vehicle-treated counterparts (Figure 6(a)). Hepatic mRNA levels of PGC-1α, CPT-1, UCP2, and UCP3 in HFD-fed hamsters were clearly lower than those of the RCD-fed group and were upregulated by ruscogenin treatment (173.2, 144.3, 163.2, and 198.3% increases, resp.) (Figure 6(a)).

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