Antiplatelet and antithrombotic activity of indole‐3‐carbinol <i>in vitro</i> and <i>in vivo</i>

Park, Min Kyu; Rhee, Yun Hee; Lee, Hyo‐Jung; Lee, Eun Ok; Kim, Kwan Hyun; Jeon, Byung Hun; Shim, Bum Sang; Jung, Chang Jin; Choi, Seung Hoon; Ahn, Kyoo Seok; Kim, Sung Hoon

doi:10.1002/ptr.2260

Cited by 38 publications

(17 citation statements)

References 22 publications

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“…the cost for lifetime management of cardiovascular risks (Barrett et al ., ). In this regard, much attention has been given to the development of herbal medicines for preventive treatment against cardiovascular diseases for their merits in safety and nature‐friendly image (Hu ; Kang et al ., ; Park et al ., ; Kloypan et al ., ). The present study has shown that EATN, a neolignan from M. fragrans , inhibited platelet aggregation induced by thrombin and PAF, without affecting platelet damage.…”

Section: Discussionmentioning

confidence: 97%

“…Anti-platelet treatment has been established as a cornerstone in the management of atherothrombotic diseases. Although several types of anti-platelet drugs are clinically utilized for the therapeutic purposes of thrombosis, natural product-derived anti-platelet agents have also been extensively investigated (Kang et al 2003;Park et al 2008;Kloypan et al 2012). A variety of natural products that possess anti-platelet activity have been reported in the literature, the majority of which are flavonoids, alkaloids, stilbenoids and phenolic compounds (Xiang et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Anti‐platelet Activity of Erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan from Myristica fragrans

Kang

Min

Lee

2013

Phytotherapy Research

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Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin- and platelet-activating factor (PAF)-induced platelet aggregation without affecting platelet damage in a concentration-dependent manner with IC50 values of 3.2 ± 0.4 and 3.4 ± 0.3 μM, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin-induced serotonin and ATP release, and thromboxane B2 formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca(2+) mobilization in thrombin-activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca(2+) mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti-platelet activity of EATN isolated from M. fragrans.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Anti‐platelet Activity of Erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan from Myristica fragrans

Kang

Min

Lee

2013

Phytotherapy Research

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“…Indole ring is another structural moiety which has been reported to have antiplatelet aggregation activity [29]. Considering this background, a diverse group of derivatives have been synthesized in this study by molecular hybridization between indole and hydrazone moieties, to find the structure–antiplatelet activity relationship of the derivatives.…”

Section: Introductionmentioning

confidence: 99%

N-Substituted indole carbohydrazide derivatives: synthesis and evaluation of their antiplatelet aggregation activity

et al. 2014

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BackgroundPlatelet aggregation is one of the most important factors in the development of thrombotic disorders which plays a central role in thrombosis (clot formation). Prophylaxis and treatment of arterial thrombosis are achieved using anti-platelet drugs. In this study, a series of novel substituted indole carbohydrazide was synthesized and evaluated for anti-platelet aggregation activity induced by adenosine diphosphate (ADP), arachidonic acid (AA) and collagen.MethodsOur synthetic route started from methyl 1H-indole-3-carboxylate (1) and ethyl 1H-indole-2-carboxylate (4) which were reacted with hydrazine monohydrate 99%. The aldol condensation of the later compound with aromatic aldehydes led to the formation of the title compounds. Sixteen indole acylhydrazone derivatives, 3d-m and 6d-i were tested for anti-platelet aggregation activity induced by adenosine diphosphate (ADP), arachidonic acid (AA) and collagen.ResultsAmong the synthesized compounds, 6g and 6h with 100% inhibition, proved to be the most potent derivatives of the 2-substituted indole on platelet aggregation induced by AA and collagen, respectively. In 3-substituted indole 3m with 100% inhibition and 3f and 3i caused 97% inhibition on platelet aggregation induced by collagen and AA, respectively.ConclusionIn this study, compounds 6g, 6h, 3m, 3f and 3i showed better inhibition on platelet aggregation induced by AA and collagen among the title compounds. Quantitative structure–activity relationship (QSAR) analysis between the structural parameters of the investigated derivatives and their antiplatelet aggregation activity was performed with various molecular descriptors but, analysis of the physicochemical parameters doesn’t show a significant correlation between the observed activities and general molecular parameters of the synthesized derivatives. Although, due to the existence of several receptors on the platelets surface which are responsible for controlling the platelet aggregation, the investigated compounds in the present study may exert their activities through binding to more than one of these receptors and therefore no straight forward SAR could be obtained for them.

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“…Recently, the consumption of polyphenol-rich foods, including vegetables and fruits, was reported to reduce the risk for acute coronary disease incidence, which was closely associated with thrombosis (Ozben et al, 2006;Park et al, 2008). Therefore, antithrombotic agent development from medicinal plants with little side effects has at-tracted much interest (Vitseva et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet and Antithrombotic Activities of Lindera obtusiloba Extract in vitro and in vivo

Lee¹,

Kim²,

Lee³

et al. 2010

Biomolecules and Therapeutics

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-Several studies have shown that plant-derived polyphenols reduce cardiovascular accidents in high-risk patients and the inhibition of platelet function may be responsible for part of this benefit. Lindera obtusiloba is widely used in traditional herbal medicine for the treatment of cardiovascular and inflammatory diseases. Therefore, the antiplatelet and antithrombotic activities of Lindera obtusiloba Extracts (LOE) on in vitro platelet aggregation, radical scavenging activity and in vivo murine pulmonary thrombosis were examined. LOE was able to directly scavenge the stable DPPH radical in a concentration-dependent manner and its IC50 value was 3.9 ± 0.1 μg/ml. LOE significantly inhibited collagen-and ADP-induced platelet aggregation in a concentration-dependent manner and its IC 50 value is 0.9 ± 0.1 mg/ml and 0.4 ± 0.1 mg/ml respectively. The inhibitory effect of LOE was comparable to aspirin (IC50 values were 1.0 ± 0.5 and 1.0 ± 0.7 mg/ml, respectively). Furthermore, oral administration of LOE suppressed the death of mice with pulmonary thrombosis induced by intravenous injection of collagen plus epinephrine. Taken together, our results suggest LOE may be a promising candidate for antithrombotic agent, and the antithrombotic effect of LOE may be due to, at least in part, antiplatelet activity.

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Antiplatelet and antithrombotic activity of indole‐3‐carbinol in vitro and in vivo

Cited by 38 publications

References 22 publications

Anti‐platelet Activity of Erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan from Myristica fragrans

Anti‐platelet Activity of Erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan from Myristica fragrans

N-Substituted indole carbohydrazide derivatives: synthesis and evaluation of their antiplatelet aggregation activity

Antiplatelet and Antithrombotic Activities of Lindera obtusiloba Extract in vitro and in vivo

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