Suppressive Effect of Maslinic Acid on PMA-induced Protein Kinase C in Human B-Lymphoblastoid Cells

Lim, Yang Mooi; Yew, Wong Teck; Yap, Wei Hsum; Soo, Khoo Kong; Hoon, Lim Saw; Yeo, Chew Chieng

doi:10.7314/apjcp.2012.13.4.1177

Cited by 11 publications

(9 citation statements)

References 32 publications

(27 reference statements)

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“…Meanwhile, others have shown that maslinic acid inhibited osteoclastogenesis by downregulating phosphorylation of MAPKs and AP-1 activity, inhibited the I κ B α phosphorylation and degradation, and blocked NF- κ B phosphorylation, nuclear translocation, and DNA-binding activity by downregulating receptor activator of NF- κ B (RANK) expression and blocking RANK interaction with tumor necrosis factor receptor-associated factor 6 (TRAF6) [ 74 ]. Maslinic acid also suppressed the expression of PKC β I, δ , and ζ in tumour promoter phorbol 12-myristate 13-acetate- (PMA-) induced Raji cell model [ 75 ]. The authors proposed that the inhibition of PKC activity by maslinic acid may explain the regulation of downstream targets in the signaling cascade including NF- κ B and downstream gene expression such as COX-2, VEGF, cyclin D1, and MMP-9 [ 14 , 75 ].…”

Section: Molecular Targets Of Maslinic Acid In Regulating Inflammamentioning

confidence: 99%

“…Maslinic acid also suppressed the expression of PKC β I, δ , and ζ in tumour promoter phorbol 12-myristate 13-acetate- (PMA-) induced Raji cell model [ 75 ]. The authors proposed that the inhibition of PKC activity by maslinic acid may explain the regulation of downstream targets in the signaling cascade including NF- κ B and downstream gene expression such as COX-2, VEGF, cyclin D1, and MMP-9 [ 14 , 75 ]. Other natural triterpenoids such as α -amyrin have been reported to inhibit PMA-induced mouse skin inflammation through suppressing PKC α [ 76 ].…”

Section: Molecular Targets Of Maslinic Acid In Regulating Inflammamentioning

confidence: 99%

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Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

Yap

Lim

2015

Biochemistry Research International

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Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs) are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX) enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS). The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB)/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli.

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Section: Molecular Targets Of Maslinic Acid In Regulating Inflammamentioning

confidence: 99%

Section: Molecular Targets Of Maslinic Acid In Regulating Inflammamentioning

confidence: 99%

Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

Yap

Lim

2015

Biochemistry Research International

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“…Inhibition of Protein kinase C (PKC) that was related to the tumor development might lead to inhibition of cells growth and spreading of cancer cells, while maslinic acid acted as a PKC inhibitor. Ursolic acid potentiated TRAIL-induced apoptosis through activation of reactive oxygen species and JNK-mediated up-regulation of death receptors and down-regulation of decoy receptor 2 and cell survival proteins [76,77]; it was also considered as a novel blocker of STAT3 activation that might have a potential in prevention and treatment of multiple myeloma and other cancers [78]. Ursolic acid and oleanolic acid possessed markedly apoptotic effects on four cell lines via increasing DNA fragmentation, decreasing mitochondrial membrane potential, lowering Na + -K + -ATPase activity and elevating caspase-3 and caspase-8 activities; they could suppress cell adhesion and reduce the production of VEGF and ICAM-1 in these cell lines [79].…”

Section: Reviewmentioning

confidence: 99%

Structural and bioactive studies of terpenes and cyclopeptides from the Genus Rubia

Wang

Yuan

et al. 2013

Chemistry Central Journal

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Genus Rubia fell into about 70 species distributed widely around the world, a total of 36 species and 2 varieties were reported from China. The extracts and phytochemicals of Rubia plants had drawn considerable attention due to their potent bioactivities. As the two major ingredients from these plants, pentacyclic triterpenes and cyclopeptides were becoming a hot topic over the past twenty years for their remarkable anticancer, antioxidant and other effects. This paper compiled all 65 terpenes and 44 cyclopeptides with their distributions, physiological activities and melting points (or optical rotations) as reported in 85 references; besides, structure-activity relationships of these derivatives were briefly discussed. The information involved in this paper was expected to be meaningful for the further studies of the Genus Rubia.

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“…Some findings have demonstrated that hGIIA-sPLA 2induced cell migration was mediated by protein kinase C (PKC) pathway [26]. Our previous study showed that maslinic acid suppresses PKC ßI, δ, and ζ activation and constitutive NF-κB activation in Raji B lymphoma cells [27]. Whether maslinic acid-mediated suppression of PKC/ NF-κB activation is dependent on inhibition of hGIIA-sPLA 2 in THP-1 monocytes requires further investigation.…”

Section: Figmentioning

confidence: 97%

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

Yap

Ahemad

Lim

2016

Lipids

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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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Suppressive Effect of Maslinic Acid on PMA-induced Protein Kinase C in Human B-Lymphoblastoid Cells

Cited by 11 publications

References 32 publications

Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

Structural and bioactive studies of terpenes and cyclopeptides from the Genus Rubia

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

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Suppressive Effect of Maslinic Acid on PMA-induced Protein Kinase C in Human B-Lymphoblastoid Cells

Cited by 11 publications

References 32 publications

Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

Structural and bioactive studies of terpenes and cyclopeptides from the Genus Rubia

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

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Product

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