Bioactive Evaluation of Ursane-Type Pentacyclic Triterpenoids: β-Boswellic Acid Interferes with the Glycosylation and Transport of Intercellular Adhesion Molecule-1 in Human Lung Adenocarcinoma A549 Cells

Abstract

Ursane-type pentacyclic triterpenoids exert various biological effects, including anticancer and anti-inflammatory activities. We previously reported that ursolic acid, corosolic acid, and asiatic acid interfered with the intracellular trafficking and glycosylation of intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with the pro-inflammatory cytokine interleukin-1α. However, the structure–activity relationship of ursane-type pentacyclic triterpenoids remains unclear. In the present study, the biological activities of seven ursane-type pentacyclic triterpenoids (β-boswellic acid, uvaol, madecassic acid, 3-O-acetyl-11-keto-β-boswellic acid, ursolic acid, corosolic acid, and asiatic acid) were investigated. We revealed that the inhibitory activities of ursane-type pentacyclic triterpenoids on the cell surface expression and glycosylation of ICAM-1 and α-glucosidase activity were influenced by the number of hydroxy groups and/or the presence and position of a carboxyl group. We also showed that β-boswellic acid interfered with ICAM-1 glycosylation in a different manner from other ursane-type pentacyclic triterpenoids.

Structure–Activity Relationship of Oleanane-Type Pentacyclic Triterpenoids on Nuclear Factor κB Activation and Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1

“…However, the molecular mechanisms by which ursolic acid and asiatic acid interfere with protein trafficking from the ER to the Golgi apparatus remain unclear. It was demonstrated that ursane-type β-boswellic acid, a structural isomer of α-boswellic acid (7), induced the accumulation of a shorter ICAM-1 protein, which conjugated to both Endo-H-sensitive and Endo-H-resistant N-glycans in a manner that differed from that of other ursane-type triterpenoids [27]. Therefore, further experiments are needed to identify the target proteins of oleanane-and ursane-type triterpenoids, which may be involved in protein trafficking in the ER to the Golgi apparatus.…”

“…In contrast to ursolic acid, oleanolic acid ( 1 ) and betulinic acid interfered with the N -glycosylation of the ICAM-1 protein but did not markedly prevent its cell surface expression [ 25 ]. The structure–activity relationship of seven ursane-type triterpenoids showed that their inhibitory activities toward the cell surface expression and N -glycosylation of ICAM-1 were affected by the number of hydroxyl groups and/or the presence and position of a carboxyl group [ 27 ]. However, the structure–activity relationship of oleanane-type triterpenoids currently remains unclear.…”

“…In our previous study, it was reported that oleanane-type, ursane-type, and lupane-type triterpenoids isolated from Nerium oleander , a small tree cultivated worldwide, interfered with the expression of ICAM-1 induced by pro-inflammatory cytokines [ 23 , 24 ]. Based on these findings, the mechanisms by which pentacyclic triterpenoids affected the protein expression, intracellular trafficking, and N -glycosylation of ICAM-1 were investigated [ 11 , 25 , 26 , 27 ]. These studies proposed that slight structural differences in pentacyclic triterpenoids markedly affected their inhibitory mechanisms.…”

Efficacy mechanisms research progress of the active components in the characteristic woody edible oils

“…Ursolic acid significantly reduces intercellular adhesion molecule‐1 cell surface expression, which is linked to pro‐inflammatory cytokines. This function of ursolic acid is related to the presence of carboxyl functional groups and the quantity of hydroxyl functional groups (Nakano et al., 2022).…”