Kuwanon G attenuates atherosclerosis by upregulation of LXRα-ABCA1/ABCG1 and inhibition of NFκB activity in macrophages

  • Toxicol Appl Pharmacol. 2018 Feb 15:341:56-63. doi: 10.1016/j.taap.2018.01.007.
Xiao-Xiao Liu  1 ,  Xiao-Wen Zhang  2 ,  Kai Wang  3 ,  Xue-Ying Wang  3 ,  Wen-Long Ma  4 ,  Wei Cao  5 ,  Dan Mo  3 ,  Yang Sun  1 ,  Xiao-Qiang Li  6
Affiliations
  • 1. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Xi'an, China.
  • 2. Department of Natural Medicine & Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
  • 3. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
  • 4. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
  • 5. Shaanxi Key Laboratory of Natural Products & Chemical Biology, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, China.
  • 6. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Xi'an, China. Electronic address: [email protected].
PMID: 29355567 DOI: 10.1016/j.taap.2018.01.007
Abstract

Background: Atherosclerosis is characterized by chronic inflammation in vascular wall. Previous studies suggest that Kuwanon G (KWG) exerts anti-inflammatory activities. However, the effect of KWG on atherosclerosis remains unexplored.

Aims: To explore whether KWG affects macrophage foam cell formation in vitro and atherogenesis in vivo.

Methods: RAW 264.7 macrophages were stimulated with ox-LDL for 24h to induce foam cell formation and treated with KWG. Foam cell formation was determined by ORO staining and enzymatic analysis. Pro-inflammatory cytokines mRNA levels were tested by Real-Time PCR method. Further molecular mechanism was investigated using Western blot. In vivo, apoE-/- mice were fed with high-fat diet and intraperitoneally injected with KWG. Atherosclerotic lesion was accessed by H&E and ORO staining. Plaque composition was evaluated by immunohistochemistry and Sirius Red staining. Serum lipid profile and inflammatory cytokines were evaluated by enzymatic method and ELISA.

Results: KWG significantly decreased intracellular lipid accumulation and inflammatory cytokines mRNA levels in macrophages through enhancing LXRα-ABCA1/ABCG1 pathway and inhibiting NFκB activation. Administrated with KWG remarkably reduced the atherosclerotic lesion areas and macrophage content in the plaque of high-fat diet fed apoE-/- mice. KWG also reduced hyperlipidemia and serum inflammatory cytokines in vivo.

Conclusion: Taken together, these data highlight that KWG can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response.

Keywords
Atherosclerosis; Foam cell formation; Inflammatory; Kuwanon G; Macrophages.
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