Potent antiplatelet activity of sesamol in an in vitro and in vivo model: pivotal roles of cyclic AMP and p38 mitogen-activated protein kinase

Chang, Chao; Lu, Wan-Jung; Chiang, Cheng-Wen; Jayakumar, Thanasekaran; Ong, Eng Thiam; Hsiao, George; Fong, Tsorng Harn; Chou, Duen Suey; Sheu, Joen Rong

doi:10.1016/j.jnutbio.2009.10.009

Cited by 31 publications

(30 citation statements)

References 25 publications

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“…In our previous report [11], sesamol (1~5 μM) exhibited potent activity of inhibiting platelet aggregation stimulated by collagen (1 μg/ml); it also significantly inhibited platelet aggregation stimulated by arachidonic acid (AA) (60 μM) at higher concentrations (5~10 μM). In the present study, we used collagen as an agonist to further explore the inhibitory mechanisms of sesamol in platelet activation.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we reported that sesamol exhibited potent activity of inhibiting platelet aggregation [11]. Its mechanism may involve an increase in the cAMP-endothelial NO synthase (eNOS)/NO-cGMP pathway, followed by inhibition of the phospholipase Cγ2 (PLCγ2)-protein kinase C (PKC)-p38 mitogen-activated protein kinase (MAPK)-thromboxane A 2 cascade, thereby leading to inhibition of [Ca 2+ ]i mobilization, and finally inhibition of platelet aggregation [11]. …”

Section: Introductionmentioning

confidence: 99%

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A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation

Chang

Ong

et al. 2011

J Biomed Sci

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BackgroundPlatelet activation is relevant to a variety of coronary heart diseases. Our previous studies revealed that sesamol possesses potent antiplatelet activity through increasing cyclic AMP formation. Although platelets are anucleated cells, they also express the transcription factor, NF-κB, that may exert non-genomic functions in platelet activation. Therefore, we further investigated the inhibitory roles of sesamol in NF-κB-mediated platelet function.MethodsPlatelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study.ResultsNF-κB signaling events, including IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation, were markedly activated by collagen (1 μg/ml) in washed human platelets, and these signaling events were attenuated by sesamol (2.5~25 μM). Furthermore, SQ22536 and ODQ, inhibitors of adenylate cyclase and guanylate cyclase, respectively, strongly reversed the sesamol (25 μM)-mediated inhibitory effects of IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation stimulated by collagen. The protein kinase A (PKA) inhibitor, H89, also reversed sesamol-mediated inhibition of IκBα degradation. Moreover, BAY11-7082, an NF-κB inhibitor, abolished IκBα degradation, phospholipase C (PLC)γ2 phosphorylation, protein kinase C (PKC) activation, [Ca2+]i mobilization, and platelet aggregation stimulated by collagen. Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca2+]i mobilization.ConclusionsSesamol activates cAMP-PKA signaling, followed by inhibition of the NF-κB-PLC-PKC cascade, thereby leading to inhibition of [Ca2+]i mobilization and platelet aggregation. Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data demonstrating that inhibition of NF-κB interferes with platelet function may have a great impact when these types of drugs are considered for the treatment of cancer and various inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation

Chang

Ong

et al. 2011

J Biomed Sci

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“…Sesamol alone, even at high concentrations (up to 1 mM) did not induce aggregation; on the other hand it was not only able to inhibit collagen-induced aggregation as reported in previous study, but also inhibited other agonist-induced (ADP and epinephrine) aggregations as evident by the present study. In an earlier study, Chang et al [8] have reported that sesamol inhibits collagen-induced platelet activation via Ca 2þ mobilization, thromboxane A 2 (TxA 2 ) formation, and phospholipase C g2 (PLC g2), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) phosphorylation. It also increases cAMP and cGMP levels, expression of endothelial nitric oxide synthase (eNOS) and NO release.…”

Section: Discussionmentioning

confidence: 99%

“…There are numerous studies of therapeutic compounds influencing platelet functions. Thereby, the present study focuses on sesamol, a therapeutic compound reported to possess potent antiplatelet activity [8]. Sesamol (3,4-methylenedioxyphenol or 1,3-benzodioxol-5-ol), a phenolic derivative of sesame seed (Sesamum indicum L.) lignans, is reported to possess antioxidant potential.…”

Section: Introductionmentioning

confidence: 99%

“…Besides, it is also used in the production of drugs for depression [11]. Recent studies have reported that sesamol in the concentration range 2.5e100 mM inhibits platelet aggregation by increasing the rate of cyclic AMP (cAMP) formation and attenuating the Nuclear Factor-kappa B (NF-kB) signaling events, thus depicting it to be an anti-thrombotic and cardioprotective compound [8,12]. However, the present study sought to demonstrate the effect of sesamol at higher concentrations on platelet functions, which is unknown hitherto.…”

Section: Introductionmentioning

confidence: 99%

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Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage

Thushara¹,

Hemshekhar²,

Sunitha³

et al. 2013

Biochimie

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Sesamol protects against liver fibrosis induced in rats by modulating lysophosphatidic acid receptor expression and TGF-β/Smad3 signaling pathway

Elrazik

El-Mesery

El‐Shishtawy

2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The present study aimed to investigate the hepatoprotective effect of sesamol (SML), a nutritional phenolic compound obtained from sesame seeds, in liver fibrosis induced by thioacetamide (TAA) in rats and to explore the underlying mechanisms. Thirty-two male Sprague–Dawley rats were equally divided into four groups: control, TAA, TAA + SML 50 mg/kg, and TAA + SML 100 mg/kg groups. Liver functions and hepatic contents of glutathione (GSH) and malondialdehyde (MDA) were measured colorimetrically. Gene expressions of lysophosphatidic acid receptor (LPAR)-1 and -3, connective tissue growth factor (CTGF), transforming growth factor (TGF)-β1, small mothers against decapentaplegic (Smad)-3 and -7, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK19) were analyzed by qRT-PCR. Moreover, phosphorylated Smad3 (pSmad3) was quantified by ELISA. Additionally, TGF-β1, α-SMA, CK19, and vascular endothelial growth factor (VEGF) protein concentrations were semi-quantitatively analyzed by immunostaining of liver sections. SML treatment markedly improved liver index and liver functions. Moreover, SML protected against liver fibrosis in a dose-dependent manner as indicated by down-regulation of LPAR1, LPAR3, CTGF, TGF-β1/Smad3, and α-SMA expressions and a decrease in pSmad3 level, as well as an up-regulation of Smad7 expression. In addition, SML suppressed ductular reaction hinted by the decrease in CK19 expression. These results reveal the anti-fibrotic effect of SML against liver fibrosis that might be attributed to down-regulation of LPAR1/3 expressions, inhibition of TGF-β1/Smad3 pathway, and ductular reaction.

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Potent antiplatelet activity of sesamol in an in vitro and in vivo model: pivotal roles of cyclic AMP and p38 mitogen-activated protein kinase

Cited by 31 publications

References 25 publications

A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation

A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation

Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage

Sesamol protects against liver fibrosis induced in rats by modulating lysophosphatidic acid receptor expression and TGF-β/Smad3 signaling pathway

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