A comparative study of the hypolipidaemic effects of a new polysaccharide, mannan Candida albicans serotype A, and atorvastatin in mice with poloxamer 407-induced hyperlipidaemia

J Pharm Pharmacol. 2016 Dec;68(12):1516-1526. doi: 10.1111/jphp.12633. Epub 2016 Oct 5.

Abstract

Objectives: We evaluated the hypolipidaemic effect of mannan Candida albicans serotype A, relative to atorvastatin, in a mouse model of hyperlipidaemia.

Methods: Mannan serotype A was investigated in vitro and in vivo to determine its effects on macrophage proliferation, nitric oxide (NO) production by cultured macrophages, serum and liver lipids, changes in liver morphology and serum chitotriosidase activity and its expression in the liver.

Key findings: Mannan serotype A stimulates the macrophage proliferation and NO production in murine peritoneal macrophages in vitro. The activity of serum chitotriosidase (an enzyme released from the activated macrophages) was found to be significantly increased in P-407-induced hyperlipidaemic mice pretreated with low-dose mannan compared with mice administered P-407 only. Mannan treatment in mice was shown to significantly increase the chitotriosidase expression in the liver of both non-hyperlipidaemic and P-407-induced hyperlipidaemic mice. Lastly, mice pretreated with mannan before the induction of hyperlipidaemia with P-407 showed a significant reduction in the serum concentration of atherogenic LDL cholesterol, total cholesterol, triglycerides and liver triglycerides.

Conclusions: It is suggested that mannan serotype A, like β-glucan, may represent another hypolipidaemic agent, which could potentially be used as an adjunctive therapy with conventional antihyperlipidaemic drugs (statins and fibrates) in humans.

Keywords: autophagy; hyperlipidaemia; macrophages; mannan; poloxamer 407.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Atorvastatin / pharmacology*
  • Biomarkers / blood
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation
  • Hexosaminidases / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hyperlipidemias / blood
  • Hyperlipidemias / chemically induced
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / pathology
  • Lipid Droplets / drug effects
  • Lipid Droplets / metabolism
  • Lipid Droplets / ultrastructure
  • Lipids / blood*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / ultrastructure
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / pathology
  • Male
  • Mannans / pharmacology*
  • Mice, Inbred CBA
  • Microscopy, Electron
  • Nitric Oxide / metabolism
  • Poloxamer*

Substances

  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Mannans
  • Poloxamer
  • Nitric Oxide
  • Atorvastatin
  • Hexosaminidases
  • chitotriosidase