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Isoflavones and phytosterols contained in Xuezhikang capsules modulate cholesterol homeostasis in high-fat diet mice.

Feng D, Sun JG, Sun RB, Ou-Yang BC, Yao L, Aa JY, Zhou F, Zhang JW, Zhang J, Wang GJ - Acta Pharmacol. Sin. (2015)

Bottom Line: Administration of F3 decreased serum TC, TG and LDL-C levels by 33%, 29% and 39%, respectively, and increased serum HDL-C by 28%, significantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPC1L1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively.Administration of F2 showed pharmacological effects similar to those of lovastatin.Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.

View Article: PubMed Central - PubMed

Affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.

ABSTRACT

Aim: Xuezhikang (XZK), an extract of red yeast rice, has been widely used in traditional Chinese medicine to treat cardiovascular disease. Three fractions F1, F2 and F3 (primarily containing isoflavones, monacolins or phytosterols, respectively) are extracted from Xuezhikang capsules. In this study we evaluated the lipid-lowering effects of these fractions and explored the potential mechanisms of actions.

Methods: Mice treated with a high-fat diet (HFD) were orally administered lovastatin (10 mg·kg(-1)·d(-1)), XZK (1200 mg·kg(-1)·d(-1)), F1 (27.5 mg·kg(-1)·d(-1)), F2 (11.3 mg·kg(-1)·d(-1)) or F3 (35 mg·kg(-1)·d(-1)) for 10 weeks. Lipids were measured using commercial enzymatic kits, and the mRNA and protein levels of genes involved in cholesterol and bile acid homeostasis were evaluated using qRT-PCR and Western blot analysis, respectively.

Results: XZK increased the fecal excretion of lipids and bile acids, reduced serum TC, TG and LDL-C levels by 40%, 55% and 46%, respectively, and increased serum HDL-C by 31%. Administration of F1 repressed serum TC and TG by 24% and 52%, respectively, and elevated hepatic synthesis of CYP7A1. It also increased hepatic elimination of bile acids in the fecal excretions by 79% through upregulating BSEP and downregulating NTCP. Administration of F3 decreased serum TC, TG and LDL-C levels by 33%, 29% and 39%, respectively, and increased serum HDL-C by 28%, significantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPC1L1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively. Administration of F2 showed pharmacological effects similar to those of lovastatin.

Conclusion: Isoflavones and phytosterols in XZK exert cholesterol-lowering effects in HFD mice through mechanisms that differ from those of lovastatin. Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.

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Related in: MedlinePlus

Hepatic and fecal lipid concentrations in high fat diet-treated C57BL/6 male mice after oral administration of lovastatin (Lv) 10 mg/kg, Xuezhikang (XZK) 1200 mg/kg, F1 (isoflavones) 27.5 mg/kg, F2 (monacolins) 11.3 mg/kg, or F3 (sterols) 35.0 mg/kg for 10 weeks, respectively. (A) Hepatic lipids; (B) Fecal lipids. Mean±SD. n=8. bP<0.05, cP<0.01 vs Control; eP<0.05, fP<0.01 vs HFD; hP<0.05, iP<0.01 vs HFD+Lv. HFD, high fat diet.
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fig3: Hepatic and fecal lipid concentrations in high fat diet-treated C57BL/6 male mice after oral administration of lovastatin (Lv) 10 mg/kg, Xuezhikang (XZK) 1200 mg/kg, F1 (isoflavones) 27.5 mg/kg, F2 (monacolins) 11.3 mg/kg, or F3 (sterols) 35.0 mg/kg for 10 weeks, respectively. (A) Hepatic lipids; (B) Fecal lipids. Mean±SD. n=8. bP<0.05, cP<0.01 vs Control; eP<0.05, fP<0.01 vs HFD; hP<0.05, iP<0.01 vs HFD+Lv. HFD, high fat diet.

Mentions: The HFD treatment resulted in significant liver weight gain (P<0.01, Table S2) and greater lipid accumulation compared with the Control group (Figure 2). HFD significantly increased serum levels of hepatic TC, FC and CE by 116%, 83% and 167%, respectively, compared to the Control group (Figure 3A).


Isoflavones and phytosterols contained in Xuezhikang capsules modulate cholesterol homeostasis in high-fat diet mice.

Feng D, Sun JG, Sun RB, Ou-Yang BC, Yao L, Aa JY, Zhou F, Zhang JW, Zhang J, Wang GJ - Acta Pharmacol. Sin. (2015)

Hepatic and fecal lipid concentrations in high fat diet-treated C57BL/6 male mice after oral administration of lovastatin (Lv) 10 mg/kg, Xuezhikang (XZK) 1200 mg/kg, F1 (isoflavones) 27.5 mg/kg, F2 (monacolins) 11.3 mg/kg, or F3 (sterols) 35.0 mg/kg for 10 weeks, respectively. (A) Hepatic lipids; (B) Fecal lipids. Mean±SD. n=8. bP<0.05, cP<0.01 vs Control; eP<0.05, fP<0.01 vs HFD; hP<0.05, iP<0.01 vs HFD+Lv. HFD, high fat diet.
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Related In: Results  -  Collection

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fig3: Hepatic and fecal lipid concentrations in high fat diet-treated C57BL/6 male mice after oral administration of lovastatin (Lv) 10 mg/kg, Xuezhikang (XZK) 1200 mg/kg, F1 (isoflavones) 27.5 mg/kg, F2 (monacolins) 11.3 mg/kg, or F3 (sterols) 35.0 mg/kg for 10 weeks, respectively. (A) Hepatic lipids; (B) Fecal lipids. Mean±SD. n=8. bP<0.05, cP<0.01 vs Control; eP<0.05, fP<0.01 vs HFD; hP<0.05, iP<0.01 vs HFD+Lv. HFD, high fat diet.
Mentions: The HFD treatment resulted in significant liver weight gain (P<0.01, Table S2) and greater lipid accumulation compared with the Control group (Figure 2). HFD significantly increased serum levels of hepatic TC, FC and CE by 116%, 83% and 167%, respectively, compared to the Control group (Figure 3A).

Bottom Line: Administration of F3 decreased serum TC, TG and LDL-C levels by 33%, 29% and 39%, respectively, and increased serum HDL-C by 28%, significantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPC1L1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively.Administration of F2 showed pharmacological effects similar to those of lovastatin.Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.

View Article: PubMed Central - PubMed

Affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.

ABSTRACT

Aim: Xuezhikang (XZK), an extract of red yeast rice, has been widely used in traditional Chinese medicine to treat cardiovascular disease. Three fractions F1, F2 and F3 (primarily containing isoflavones, monacolins or phytosterols, respectively) are extracted from Xuezhikang capsules. In this study we evaluated the lipid-lowering effects of these fractions and explored the potential mechanisms of actions.

Methods: Mice treated with a high-fat diet (HFD) were orally administered lovastatin (10 mg·kg(-1)·d(-1)), XZK (1200 mg·kg(-1)·d(-1)), F1 (27.5 mg·kg(-1)·d(-1)), F2 (11.3 mg·kg(-1)·d(-1)) or F3 (35 mg·kg(-1)·d(-1)) for 10 weeks. Lipids were measured using commercial enzymatic kits, and the mRNA and protein levels of genes involved in cholesterol and bile acid homeostasis were evaluated using qRT-PCR and Western blot analysis, respectively.

Results: XZK increased the fecal excretion of lipids and bile acids, reduced serum TC, TG and LDL-C levels by 40%, 55% and 46%, respectively, and increased serum HDL-C by 31%. Administration of F1 repressed serum TC and TG by 24% and 52%, respectively, and elevated hepatic synthesis of CYP7A1. It also increased hepatic elimination of bile acids in the fecal excretions by 79% through upregulating BSEP and downregulating NTCP. Administration of F3 decreased serum TC, TG and LDL-C levels by 33%, 29% and 39%, respectively, and increased serum HDL-C by 28%, significantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPC1L1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively. Administration of F2 showed pharmacological effects similar to those of lovastatin.

Conclusion: Isoflavones and phytosterols in XZK exert cholesterol-lowering effects in HFD mice through mechanisms that differ from those of lovastatin. Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.

Show MeSH
Related in: MedlinePlus