Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1

Biol Pharm Bull. 2018;41(12):1757-1768. doi: 10.1248/bpb.b18-00276.

Abstract

The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus. In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1. In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface. Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells. Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein. Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker). Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity. These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.

Keywords: asiatic acid; corosolic acid; intercellular adhesion molecule-1; intracellular trafficking; maslinic acid; pentacyclic triterpenoid.

MeSH terms

  • A549 Cells
  • Cytokines / immunology
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism*
  • Glycosylation / drug effects*
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / immunology
  • Golgi Apparatus / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Microscopy, Confocal
  • Pentacyclic Triterpenes / pharmacology*
  • Polysaccharides / metabolism
  • Protein Transport
  • Triterpenes / pharmacology*

Substances

  • Cytokines
  • Pentacyclic Triterpenes
  • Polysaccharides
  • Triterpenes
  • Intercellular Adhesion Molecule-1
  • asiatic acid
  • corosolic acid
  • maslinic acid