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Inhibition of Human Group IIA‐Secreted Phospholipase A 2 and THP‐1 Monocyte Recruitment by Maslinic Acid
Author(s) -
Yap Wei Hsum,
Ahmed Nafees,
Lim Yang Mooi
Publication year - 2016
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-016-4186-1
Subject(s) - enzyme , biochemistry , chemistry , phospholipase a2 , phospholipid , phospholipase , monocyte , phospholipase a , arachidonic acid , membrane , biology , immunology
Maslinic acid is a natural pentacyclic triterpenoid which has anti‐inflammatory properties. A recent study showed that secretory phospholipase A 2 (sPLA 2 ) may be a potential binding target of maslinic acid. The human group IIA (hGIIA)‐sPLA 2 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‐sPLA 2 and inhibits inflammatory response induced by this enzyme. It is shown that maslinic acid enhanced intrinsic fluorescence of hGIIA‐sPLA 2 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‐sPLA 2 enzyme is also responsible in mediating monocyte recruitment and differentiation. Results showed that maslinic acid inhibit hGIIA‐sPLA 2 ‐induced THP‐1 cell differentiation and migration, and the effect observed is specific to hGIIA‐sPLA 2 as cells treated with maslinic acid alone did not significantly affect the number of adherent and migrated cells. Considering that hGIIA‐sPLA 2 enzyme is known to hydrolyze glyceroacylphospholipids present in lipoproteins and cell membranes, maslinic acid may bind and inhibit hGIIA‐sPLA 2 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‐sPLA 2 as well as its effect towards hGIIA‐sPLA 2 ‐induced THP‐1 monocyte adhesive and migratory capabilities, an important immune‐inflammation process in atherosclerosis.