Maslinic acid modulates secreted phospholipase A₂-IIA (sPLA₂-IIA)-mediated inflammatory effects in macrophage foam cells formation

Secretory phospholipase A₂-IIA (sPLA₂-IIA) is one of the key enzymes causing lipoprotein modification and vascular inflammation. Maslinic acid is a pentacyclic triterpene which has potential cardioprotective and anti-inflammatory properties. Recent research showed that maslinic acid interacts with sPLA₂-IIA and inhibits sPLA₂-IIA-mediated monocyte differentiation and migration. This study elucidates the potential of maslinic acid in modulating sPLA₂-IIA-mediated inflammatory effects in THP-1 macrophages. We showed that maslinic acid inhibits sPLA₂-IIA-mediated LDL modification and suppressed foam cell formation. Further analysis revealed that sPLA₂-IIA only induced modest LDL oxidation and that inhibitory effect of maslinic acid on sPLA₂-IIA-mediated foam cells formation occurred independently of its anti-oxidative properties. Interestingly, maslinic acid was also found to significantly reduce lipid accumulation observed in macrophages treated with sPLA₂-IIA only. Flow cytometry analysis demonstrated that the effect observed in maslinic acid might be contributed in part by suppressing sPLA₂-IIA-induced endocytic activity, thereby inhibiting LDL uptake. The study further showed that maslinic acid suppresses sPLA₂-IIA-induced up-regulation of PGE₂ levels while having no effects on COX-2 activity. Other pro-inflammatory mediators TNF-α and IL-6 were not induced in sPLA₂-IIA-treated THP-1 macrophages. The findings of this study showed that maslinic acid inhibit inflammatory effects induced by sPLA₂-IIA, including foam cells formation and PGE₂ production.