Yap Wei Hsum, Ahmed Nafees, Lim Yang Mooi
School of Biosciences, Taylor's University, Subang Jaya, Selangor, Malaysia.
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Petaling, Selangor, Malaysia.
Lipids. 2016 Oct;51(10):1153-1159. doi: 10.1007/s11745-016-4186-1. Epub 2016 Aug 19.
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.
山楂酸是一种具有抗炎特性的天然五环三萜类化合物。最近的一项研究表明，分泌型磷脂酶A2（sPLA2）可能是山楂酸的潜在结合靶点。人类IIA组（hGIIA）-sPLA2存在于人体血清中，其水平与炎症严重程度相关。本研究旨在确定山楂酸是否与hGIIA-sPLA2相互作用，并抑制该酶诱导的炎症反应。结果表明，山楂酸增强了hGIIA-sPLA2的内在荧光，并以浓度依赖的方式抑制其酶活性。分子对接显示，山楂酸与钙结合和界面磷脂结合位点结合，表明它抑制催化钙离子进入酶促反应，并阻止酶与膜磷脂的结合。hGIIA-sPLA2酶还负责介导单核细胞的募集和分化。结果表明，山楂酸抑制hGIIA-sPLA2诱导的THP-1细胞分化和迁移，观察到的效果对hGIIA-sPLA2具有特异性，因为单独用山楂酸处理的细胞对贴壁和迁移细胞的数量没有显著影响。鉴于已知hGIIA-sPLA2酶可水解脂蛋白和细胞膜中存在的甘油酰磷脂，山楂酸可能结合并抑制hGIIA-sPLA2的酶活性，从而减少刺激单核细胞迁移和分化的脂肪酸和溶血磷脂的释放。本研究首次报道了山楂酸与炎症靶点hGIIA-sPLA2之间的分子相互作用，以及其对hGIIA-sPLA2诱导的THP-1单核细胞黏附和迁移能力的影响，这是动脉粥样硬化中一个重要的免疫炎症过程。
