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Inhibition of Human Group IIA-Secreted Phospholipase A2 and THP-1 Monocyte Recruitment by Maslinic Acid

  • Original Article
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Lipids

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.

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Abbreviations

hGIIA-sPLA2 :

Human Group IIA-secreted phospholipase A2

β-Py-C10-PG:

1-Hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphoglycerol Ammonium salt

PC:

Phosphatidylcholine

NEFA:

Non-esterified fatty acid

NF-κB:

Nuclear factor-kappa B

PKC:

Protein kinase C

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Acknowledgments

The authors would like to thank Taylor’s University for funding support (Taylor’s Research Grant Scheme TRGS/ERFS/1/2014/SBS/013).

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Authors and Affiliations

  1. School of Biosciences, Taylor’s University, Subang Jaya, Selangor, Malaysia

    Wei Hsum Yap

  2. Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Petaling, Selangor, Malaysia

    Nafees Ahmed

  3. Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia

    Yang Mooi Lim

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  1. Wei Hsum Yap
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  2. Nafees Ahmed
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Correspondence to Wei Hsum Yap.

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Electronic supplementary material

Below is the link to the electronic supplementary material.

11745_2016_4186_MOESM1_ESM.pdf

Supplementary Figure 1: Characterization of hGIIA-sPLA2 enzyme inhibition by maslinic acid. Lineweaver–Burk plots of hGIIA-sPLA2 enzyme kinetics analysis with substrate β-py-C10-PG (from 0.625 to 20 µM) in the absence (no inhibitor) and presence of maslinic acid (100 µM). (PDF 34 kb)

11745_2016_4186_MOESM2_ESM.pdf

Supplementary Figure 2: Effect of maslinic acid on THP-1 cell adhesion. THP-1 cells were either untreated or treated with various concentrations of maslinic acid (5, 10, 20 and 50 µM). The cells were incubated at 37°C for 24 h, and the number of adherent cells was determined as indicated in Materials and methods. Each bar represents mean number of adherent cells of three independent experiments ± SD; n = 3. (PDF 68 kb)

11745_2016_4186_MOESM3_ESM.pdf

Supplementary Figure 3: Effect of maslinic acid on THP-1 cell migration. THP-1 cells were either untreated or treated with various concentrations of maslinic acid (5, 10, 20 and 50 µM). The cells were incubated at 37°C for 24 h, and the number of cells migrated were determined as indicated in Materials and methods. Each bar represents mean number of migrated cells of three independent experiments ± SD; n = 3. (PDF 492 kb)

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Yap, W.H., Ahmed, N. & Lim, Y.M. Inhibition of Human Group IIA-Secreted Phospholipase A2 and THP-1 Monocyte Recruitment by Maslinic Acid. Lipids 51, 1153–1159 (2016). https://doi.org/10.1007/s11745-016-4186-1

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  • DOI: https://doi.org/10.1007/s11745-016-4186-1

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