Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of...Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS （40 or 80 mg · kg^-1 ） was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H＆E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 （ SREBP-1 ）, fatty acid synthase （FASN） and acetyl-CoA carboxylase （ACC） in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase （AMPK） and liver kinase B1 （LKB1）. Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL （PPARoL） protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.展开更多
OBJECTIVE Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis.We investigated whether this process would be modulated by gentiopicroside(GPS),whi...OBJECTIVE Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis.We investigated whether this process would be modulated by gentiopicroside(GPS),which is attributed to the bitterness of gentian root extract.METHODS An in vivo model was established by intragastrically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with ethanol or treating RAW 264.7 macrophages and murine bone marrow-derived macrophages(BMDMs) with lipopolysaccharides(LPS) plus adenosine triphos.phate(ATP).RESULTS In alcoholic hepatosteatotic mice model,GPS decreased serum aminotrans.ferase and triglyceride accumulation.GPS regulated sterol regulatory element-binding protein-1(Srebp1),peroxisome proliferators-actived receptors α(PPARα) and acetyl CoA carboxylase(ACC) expression via elevating liver kinase B1(LKB1)/AMP-activated Kinase(AMPK).Suppression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 and expression by GPS resulted in the inhibition of interleukin-1β(IL-1β) production.In ethanol-exposed HepG2 cells,GPS reduced lipo.genesis and promoted lipid oxidation via P2x7R-NLRP3 inflammasome activation.P2x7R silencing enhanced AMPK activity,and reduced Srebp1 expression in ethanol-treated hepatocytes.GPS down.regulated P2x7R-mediated inflammatory response to extracellular ATP in LPS-primed RAW 264.7 macro.phages and BMDMs.Additionally,P2x7R deficiency attenuated IL-1β cleavage in RAW 264.7 macro.phages,and GPS further suppressed IL-1β cleavage.CONCLUSION Activation of LKB1/AMPK signaling by GPS might be mediated by P2x7R-NLRP3 inflammasome,suggesting a therapeutic utility of P2x7R blockade in alcoholic hepatosteatosis treatment.展开更多
OBJECTIVE Dihydroquercetin(TAX) is the most abundant dihydroflavone found in on.ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in v...OBJECTIVE Dihydroquercetin(TAX) is the most abundant dihydroflavone found in on.ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro.METHODS An in vivo model was established by intragas.trically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with etha.nol.RESULTS TAX regulated Sterol Regulatory Element-binding Protein-1(SREBP1) and Acetyl CoA Carboxylase(ACC) expression via elevating Liver Kinase B1(LKB1)/AMP-activated Kinase(AMPK)phosphorylation.Also,TAX upregulated SIRT1 expression,which suppressed by ethanal intake.Suppression of Purinergic 2X7 receptor(P2x7R),nucleotide-binding oligomerization domain-like re.ceptor protein 3(NLRP3) and Cysteine protease-1(caspase-1) cleavage by TAX resulted in the inhibi.tion of Interleukin-1β(IL-1β) production and release.Additionally,TAX reduced lipogenesis and pro.moted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cell.TAX downregulated IL-1β cleavage response to Lipopolysaccharides(LPS) plus adenosine triphosphate(ATP) stimulation in HepG2 cells.P2x7R deficiency attenuated lipid accumulation with increasing AMPK activity and decreasing SREBP1 expression in ethanol-treated HepG2 cells.CONCLUSION Our data showed that TAX exhibited the inhibitory properties on lipogenesis and hepatoprotective ca.pacity,indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.展开更多
文摘Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS （40 or 80 mg · kg^-1 ） was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H＆E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 （ SREBP-1 ）, fatty acid synthase （FASN） and acetyl-CoA carboxylase （ACC） in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase （AMPK） and liver kinase B1 （LKB1）. Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL （PPARoL） protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.
基金supported by National Natural Science Foundation of China(8156059781260664+1 种基金8136065881660689)
文摘OBJECTIVE Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis.We investigated whether this process would be modulated by gentiopicroside(GPS),which is attributed to the bitterness of gentian root extract.METHODS An in vivo model was established by intragastrically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with ethanol or treating RAW 264.7 macrophages and murine bone marrow-derived macrophages(BMDMs) with lipopolysaccharides(LPS) plus adenosine triphos.phate(ATP).RESULTS In alcoholic hepatosteatotic mice model,GPS decreased serum aminotrans.ferase and triglyceride accumulation.GPS regulated sterol regulatory element-binding protein-1(Srebp1),peroxisome proliferators-actived receptors α(PPARα) and acetyl CoA carboxylase(ACC) expression via elevating liver kinase B1(LKB1)/AMP-activated Kinase(AMPK).Suppression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 and expression by GPS resulted in the inhibition of interleukin-1β(IL-1β) production.In ethanol-exposed HepG2 cells,GPS reduced lipo.genesis and promoted lipid oxidation via P2x7R-NLRP3 inflammasome activation.P2x7R silencing enhanced AMPK activity,and reduced Srebp1 expression in ethanol-treated hepatocytes.GPS down.regulated P2x7R-mediated inflammatory response to extracellular ATP in LPS-primed RAW 264.7 macro.phages and BMDMs.Additionally,P2x7R deficiency attenuated IL-1β cleavage in RAW 264.7 macro.phages,and GPS further suppressed IL-1β cleavage.CONCLUSION Activation of LKB1/AMPK signaling by GPS might be mediated by P2x7R-NLRP3 inflammasome,suggesting a therapeutic utility of P2x7R blockade in alcoholic hepatosteatosis treatment.
基金supported by National Natural Science Foundation of China(8156059781260664+1 种基金81360658and 81660689)
文摘OBJECTIVE Dihydroquercetin(TAX) is the most abundant dihydroflavone found in on.ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro.METHODS An in vivo model was established by intragas.trically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with etha.nol.RESULTS TAX regulated Sterol Regulatory Element-binding Protein-1(SREBP1) and Acetyl CoA Carboxylase(ACC) expression via elevating Liver Kinase B1(LKB1)/AMP-activated Kinase(AMPK)phosphorylation.Also,TAX upregulated SIRT1 expression,which suppressed by ethanal intake.Suppression of Purinergic 2X7 receptor(P2x7R),nucleotide-binding oligomerization domain-like re.ceptor protein 3(NLRP3) and Cysteine protease-1(caspase-1) cleavage by TAX resulted in the inhibi.tion of Interleukin-1β(IL-1β) production and release.Additionally,TAX reduced lipogenesis and pro.moted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cell.TAX downregulated IL-1β cleavage response to Lipopolysaccharides(LPS) plus adenosine triphosphate(ATP) stimulation in HepG2 cells.P2x7R deficiency attenuated lipid accumulation with increasing AMPK activity and decreasing SREBP1 expression in ethanol-treated HepG2 cells.CONCLUSION Our data showed that TAX exhibited the inhibitory properties on lipogenesis and hepatoprotective ca.pacity,indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.
