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编 号：F762333
分子式：C27H46O5S
分子量：482.72
分子式：C27H46O5S
分子量：482.72
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CAS No: 884905-07-1
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生物活性：
Larsucosterol (DUR-928), a cholesterol metabolite, is a potent liver X receptor (LXR) antagonist. Larsucosterol as a potent endogenous regulator decreases lipogenesis. Larsucosterol inhibits the cholesterol biosynthesis via decreasing mRNA levels and inhibiting the activation of SREBP-1.
体内研究：
Larsucosterol (DUR-928; 25 mg/kg; i.p.; twice in 14 hours; C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model) reduces serum lipid levels in mice fed a high-fat diet.Larsucosterol (25 mg/kg; i.p.; twice in 14 hours; C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model) suppressed the expression of the genes and inhibits ABCA1 expressionde. Larsucosterolcreases nuclear SREBP-1 Protein levels and cytoplasmic FAS and ACC1 protein levels in liver tissue.Larsucosterol (25 mg/kg; i.p.; once every 3 days for 6 weeks; C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model) protects the liver from injury by suppressing hepatic inflammation.Animal Model:Female C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model
Dosage:25 mg/kg
Administration:Intraperitoneal injection; once every 3 days for 6 weeks
Result:Decreased plasma cholesterol levels.Reduced serum alkaline phosphatase, ALT, and AST levels.
Animal Model:Female C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model
Dosage:25 mg/kg
Administration:Intraperitoneal injection; twice in 14 hours
Result:Decreased plasma TG, CHOL, and HDL-C by 40, 15, and 20%, respectively.Reduced the mRNA levels of SREBP-1c, ACC1, and FAS by 46, 57, and 49%, respectively.Suppressed ABCA1 expression.Suppressed nuclear SREBP-1, cytoplasmic ACC1, and FAS protein levels by 74, 58, and 47%, respectively.
体外研究：
Larsucosterol (DUR-928; 0-25 μM; 8 h; HepG2 cells) inhibits cholesterol biosynthesis by decreasing HMG-CoA reductase mRNA levels and decreases free [14C] cholesterol in a dose-dependent manner.Larsucosterol (0-25 μM; 6 h; HepG2 cells) inhibits HMG-CoA reductase expression by inhibition of both SREBP1 activation and expression in hepatocytes.Larsucosterol (0-50 μM; 48 h) increases cell proliferation and decreases apoptosis in macrophages.Larsucosterol (0-25 μM; 48 h; macrophages) inhibits activation of liver oxysterol receptor LXRα.
Larsucosterol (DUR-928), a cholesterol metabolite, is a potent liver X receptor (LXR) antagonist. Larsucosterol as a potent endogenous regulator decreases lipogenesis. Larsucosterol inhibits the cholesterol biosynthesis via decreasing mRNA levels and inhibiting the activation of SREBP-1.
体内研究：
Larsucosterol (DUR-928; 25 mg/kg; i.p.; twice in 14 hours; C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model) reduces serum lipid levels in mice fed a high-fat diet.Larsucosterol (25 mg/kg; i.p.; twice in 14 hours; C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model) suppressed the expression of the genes and inhibits ABCA1 expressionde. Larsucosterolcreases nuclear SREBP-1 Protein levels and cytoplasmic FAS and ACC1 protein levels in liver tissue.Larsucosterol (25 mg/kg; i.p.; once every 3 days for 6 weeks; C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model) protects the liver from injury by suppressing hepatic inflammation.Animal Model:Female C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model
Dosage:25 mg/kg
Administration:Intraperitoneal injection; once every 3 days for 6 weeks
Result:Decreased plasma cholesterol levels.Reduced serum alkaline phosphatase, ALT, and AST levels.
Animal Model:Female C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model
Dosage:25 mg/kg
Administration:Intraperitoneal injection; twice in 14 hours
Result:Decreased plasma TG, CHOL, and HDL-C by 40, 15, and 20%, respectively.Reduced the mRNA levels of SREBP-1c, ACC1, and FAS by 46, 57, and 49%, respectively.Suppressed ABCA1 expression.Suppressed nuclear SREBP-1, cytoplasmic ACC1, and FAS protein levels by 74, 58, and 47%, respectively.
体外研究：
Larsucosterol (DUR-928; 0-25 μM; 8 h; HepG2 cells) inhibits cholesterol biosynthesis by decreasing HMG-CoA reductase mRNA levels and decreases free [14C] cholesterol in a dose-dependent manner.Larsucosterol (0-25 μM; 6 h; HepG2 cells) inhibits HMG-CoA reductase expression by inhibition of both SREBP1 activation and expression in hepatocytes.Larsucosterol (0-50 μM; 48 h) increases cell proliferation and decreases apoptosis in macrophages.Larsucosterol (0-25 μM; 48 h; macrophages) inhibits activation of liver oxysterol receptor LXRα.
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