title: Inhibition of Human Group IIA-Secreted Phospholipase A2 and THP-1 Monocyte Recruitment by Maslinic Acid.
abstract: Maslinic acid is a natural pentacyclic triterpenoid which has anti-inflammatory properties. A recent study showed that secretory phospholipase A2 (sPLA2) may be a potential binding target of maslinic acid. The human group IIA (hGIIA)-sPLA2 is found in human sera and their levels are correlated with severity of inflammation. This study aims to determine whether maslinic acid interacts with hGIIA-sPLA2 and inhibits inflammatory response induced by this enzyme. It is shown that maslinic acid enhanced intrinsic fluorescence of hGIIA-sPLA2 and inhibited its enzyme activity in a concentration-dependent manner. Molecular docking revealed that maslinic acid binds to calcium binding and interfacial phospholipid binding site, suggesting that it inhibit access of catalytic calcium ion for enzymatic reaction and block binding of the enzyme to membrane phospholipid. The hGIIA-sPLA2 enzyme is also responsible in mediating monocyte recruitment and differentiation. Results showed that maslinic acid inhibit hGIIA-sPLA2-induced THP-1 cell differentiation and migration, and the effect observed is specific to hGIIA-sPLA2 as cells treated with maslinic acid alone did not significantly affect the number of adherent and migrated cells. Considering that hGIIA-sPLA2 enzyme is known to hydrolyze glyceroacylphospholipids present in lipoproteins and cell membranes, maslinic acid may bind and inhibit hGIIA-sPLA2 enzymatic activity, thereby reduces the release of fatty acids and lysophospholipids which stimulates monocyte migration and differentiation. This study is the first to report on the molecular interaction between maslinic acid and inflammatory target hGIIA-sPLA2 as well as its effect towards hGIIA-sPLA2-induced THP-1 monocyte adhesive and migratory capabilities, an important immune-inflammation process in atherosclerosis.
authors.affiliation: School of Biosciences, Taylor's University, Subang Jaya, Selangor, Malaysia. weihsum.yap@taylors.edu.my.
authors.forename: Wei Hsum
authors.identifier: 0000-0001-8116-6018
authors.initials: WH
authors.lastname: Yap
authors.affiliation: Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Petaling, Selangor, Malaysia.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia.
authors.forename: Yang Mooi
authors.initials: YM
authors.lastname: Lim
mesh_terms: D002118:Calcium / Q000378:metabolism; D020134:Catalytic Domain / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D062105:Molecular Docking Simulation; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D014315:Triterpenes / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D002118:Calcium; D054501:Group II Phospholipases A2; D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid
keywords: Immunology; Inflammation; Lipases; Phospholipase A2; Physiology