[Effects of Chinese herbal medicine Guanxinkang on expression of PPARγ-LXRα-ABCA1 pathway in ApoE-knockout mice with atherosclerosis].

OBJECTIVE: To observe the effects of Guanxinkang (GXK) decoction, a compound traditional Chinese herbal medicine, on expressions of peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα) and ATP-binding cassette transporter A1 (ABCA1) in apolipoprotein E (ApoE)-knockout mice with atherosclerosis. METHODS: Fourteen 6-week-old C57BL/6 J mice were used as normal control group. Seventy 6-week-old ApoE-knockout mice receiving a high-cholesterol diet to induce atherosclerosis were randomly divided into untreated group, simvastatin group and low-dose (concentration of crude drugs at 0.864 g/mL), medium-dose (crude drugs at 1.728 g/mL) and high-dose (crude drugs at 3.456 g/mL) GXK groups. After treated with the drugs for eight weeks continuously, the livers and aortas of mice were separated. The expressions of PPARγ, LXRα and ABCA1 were measured by real-time quantitative polymerase chain reaction and Western blotting respectively. RESULTS: Compared with the normal control group, mRNAs and proteins of PPARγ, LXRα and ABCA1 over-expressed in the untreated group (P<0.05). After the treatment, GXK decoction and simvastatin decreased the expressions of PPARγ, LXRα and ABCA1 (P<0.05). High-dose GXK decoction had more marked effects than low- and medium-dose GXK and simvastatin. CONCLUSION: The PPARγ-LXRα-ABCA1 pathway is involved in lipid regulation and inflammation activities. Over-expression of the genes has complicated effects on atherosclerosis in ApoE-knockout mice with high-cholesterol diet. GXK decoction has anti-inflammatory and anti-matrix metalloproteinase activities by regulating PPARγ, LXRα and ABCA1 interactions in the ApoE-knockout mice.

[Effects of Chinese herbal medicine Guanxinkang on lipid metabolism and serum C-reactive protein, amyloid A protein and fibrinogen in apolipoprotein E-knockout mice with atherosclerosis].

OBJECTIVE: To observe the effects of Guanxinkang (GXK) decoction, a compound traditional Chinese herbal medicine, on serum lipids and apolipoprotein A I (ApoA I), apolipoprotein B (ApoB), apolipoprotein E (ApoE), C-reactive protein (CRP), serum amyloid A protein (SAA) and fibrinogen (Fbg) concentrations of ApoE-knockout mice with atherosclerosis, and to explore the mechanism of GXK decoction in anti-atherosclerosis. METHODS: Seventy 6-week-old ApoE-knockout mice receiving a high-cholesterol diet were used to induce atherosclerosis and were randomly divided into 5 groups: untreated group, simvastatin group and low- (drug concentration is 0.864 g/mL), medium- (1.728 g/mL), and high-dose (3.456 g/mL) GXK groups. Another fourteen 6-week-old C57BL/6J mice were used as the normal control. Two 12-week-old mice were randomly selected from the normal control and the ApoE-knockout mice respectively to observe vulnerable plaque in the mouse's aortic by hematoxylin-eosin staining. Blood was collected from venous plexus of eye socket after gavage of corresponding drugs once daily for 8 weeks continuously, and then the serum was separated. Triglyceride (TAG) and total cholesterol (TC) were measured by enzyme-coupled assay; low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by selective precipitation method. Serum levels of ApoA I and ApoB were determined by turbidimetry. Double-antibody sandwich enzyme-linked immunosorbent assay was used to detect ApoE, CRP, SAA and Fbg concentrations in serum. RESULTS: Compared with the normal control group, the levels of serum TC, TAG, LDL-C, ApoB, CRP, SAA and Fbg in the untreated group were increased (P<0.05), and the serum concentrations of HDL-C, ApoA I and ApoE in the untreated group were decreased (P<0.05). After treatment, GXK decoction and simvastatin improved the dyslipidemia by increasing the concentrations of ApoA I and HDL-C and decreasing the concentrations of TC, TAG, LDL-C, ApoB, CRP, SAA and Fbg (P<0.05). The high-dose GXK decoction had the most marked effects on SAA and Fbg and the serum lipids compared with the low-dose and medium-dose GXK and simvastatin. CONCLUSION: GXK decoction may not only provide an active effect on hyperlipidemia, but also down-regulate the levels of serum CRP, SAA and Fbg. GXK decoction exerts an anti-atherosclerosis effect in ApoE-knockout mice.