Effect of Combined Use of Astragaloside IV (AsIV) and Atorvastatin (AV) on Expression of PPAR-γ and Inflammation-Associated Cytokines in Atherosclerosis Rats.

Abstract

BACKGROUND The aim of this study was to assess the effect of combined use of Astragaloside IV(AsIV) and atorvastatin (AV) on the expression of PPAR-γ and inflammation-associated cytokines in atherosclerosis rats. MATERIAL AND METHODS High-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma were detected through automatic biochemical analyzer and the histopathological analysis was performed via HE staining. The levels of oxidized low-density lipoprotein (oxLDL) and tumor necrosis factor-α (TNF-α), and interleukins (IL)-6 and IL-18 in serum were detected by ELISA. The expressions of proliferator-activated receptor-gamma (PPAR-γ), cluster of differentiation 36 (CD36), matrix metalloprotein-9 (MMP-9), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1), and p38 and P-p38 levels were detected by Western blot. RT-PCR was used to detect the mRNA expressions of nuclear factor-κB (NF-κB), PPAR-γ, CD36, MMP-9, ICAM-1, and VCAM-1. RESULTS Administration of AsIV and AV significantly decreased the lipid content and oxLDL in plasma. The levels of TNF-α, IL-6, and IL-18 were significantly decreased in AsIV, AV, and AsIV + AV groups, especially in the AsIV + AV group. Administration decreased the levels of NF-κB, CD36, MMP-9, ICAM-1, VCAM-1, and P-p38 expression and increased the expression of peroxisome PPAR-γ. Compared with the NC group, the atherosclerotic lesions significantly increased in the HD group, while the combined administration significantly inhibited the development of atherosclerotic disease. CONCLUSIONS Combined administration of AV and AsIV showed potent effects against atherosclerosis through the NF-κB/PPARγ pathway, which may be a new therapy for treatment of atherosclerosis in the future.

• Authors: Bin Sun, Ruping Rui, Haiying Pan, Luchang Zhang, Xiaolong Wang
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 24 Pg. 6229-6236 (Sep 07 2018) ISSN: 1643-3750 [Electronic] United States
• PMID: 30190450 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Interleukin-18
• Interleukin-6
• Lipoproteins, HDL
• Lipoproteins, LDL
• PPAR gamma
• PPAR gamma, rat
• Saponins
• Triterpenes
• Tumor Necrosis Factor-alpha
• oxidized low density lipoprotein
• astragaloside A
• Atorvastatin

Topics

• Animals
• Atherosclerosis (drug therapy)
• Atorvastatin (pharmacology)
• China
• Cytokines (drug effects)
• Disease Models, Animal
• Drug Therapy, Combination (methods)
• Inflammation (metabolism)
• Interleukin-18 (metabolism)
• Interleukin-6 (metabolism)
• Lipoproteins, HDL (blood)
• Lipoproteins, LDL (blood)
• Male
• PPAR gamma (drug effects)
• Rats
• Rats, Sprague-Dawley
• Saponins (pharmacology)
• Signal Transduction (drug effects)
• Triterpenes (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)