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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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Structure of ruscogenin.
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fig1: Structure of ruscogenin.

Mentions: Ruscogenin ((1β, 3β, 25R)-Spirost-5-ene-1,3-diol; Figure 1) is a major effective steroidal sapogen in the traditional Chinese herb Radix Ophiopogon japonicus, that has been used to treat acute and chronic inflammatory and cardiovascular diseases [7, 8]. Ruscogenin has been found to exert significant anti-inflammatory activities in many aspects such as antielastase activity, inhibiting leukocyte adhesion and migration, and antithrombotic activity [9–11]. Previous research has proved that the possible anti-inflammatory mechanism of ruscogenin was linked with the suppression of intercellular adhesion molecule-1 expression in endothelial cells mainly through the inhibition of the NF-κB signaling pathway [12]. It was also found that ruscogenin significantly attenuated lipopolysaccharide- (LPS-) induced acute lung injury model in mice, which possibly linked with inhibition of NF-κB activation [13]. Ruscogenin has also been documented to reduce cerebral ischemic injury via NF-κB mediated inflammatory pathway in the mouse model of experimental stroke. [14]. Downregulation of NF-κB-mediated inflammatory responses induced by ruscogenin may indicate its potential protection in NASH; however, there is no report about it until now. Therefore, the aim of the present study was to investigate the protective effects of ruscogenin supplementation on liver steatosis and injury in hamsters fed a high-fat diet (HFD). These effects of ruscogenin were further characterized in HepG2 hepatocytes.


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)

Structure of ruscogenin.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Structure of ruscogenin.
Mentions: Ruscogenin ((1β, 3β, 25R)-Spirost-5-ene-1,3-diol; Figure 1) is a major effective steroidal sapogen in the traditional Chinese herb Radix Ophiopogon japonicus, that has been used to treat acute and chronic inflammatory and cardiovascular diseases [7, 8]. Ruscogenin has been found to exert significant anti-inflammatory activities in many aspects such as antielastase activity, inhibiting leukocyte adhesion and migration, and antithrombotic activity [9–11]. Previous research has proved that the possible anti-inflammatory mechanism of ruscogenin was linked with the suppression of intercellular adhesion molecule-1 expression in endothelial cells mainly through the inhibition of the NF-κB signaling pathway [12]. It was also found that ruscogenin significantly attenuated lipopolysaccharide- (LPS-) induced acute lung injury model in mice, which possibly linked with inhibition of NF-κB activation [13]. Ruscogenin has also been documented to reduce cerebral ischemic injury via NF-κB mediated inflammatory pathway in the mouse model of experimental stroke. [14]. Downregulation of NF-κB-mediated inflammatory responses induced by ruscogenin may indicate its potential protection in NASH; however, there is no report about it until now. Therefore, the aim of the present study was to investigate the protective effects of ruscogenin supplementation on liver steatosis and injury in hamsters fed a high-fat diet (HFD). These effects of ruscogenin were further characterized in HepG2 hepatocytes.

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