A novel selective inhibitor to thrombin-induced platelet aggregation purified from the leech Whitmania pigra

Li, Xuan; Wang, Caihui; Ding, Xue; Liu, Xiaodong; Li, Qian; Kong, Yi

doi:10.1016/j.bbrc.2016.03.117

Cited by 28 publications

(13 citation statements)

References 27 publications

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“…Whitmania pigra Whitman, etc. (Feng et al, 2012; Lu M. et al, 2015; Lu Y. et al, 2015; Liu et al, 2016). Xiao et al (2012) identified two PAI-1 inhibitors, tanshinone IIA and cryptotanshinone, from Salvia miltiorrhiza Bge , and inhibition of PAI-1 was considered to be one of the mechanism by which Salvia miltiorrhiza Bge exerts its anticoagulant effect.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of PAI-1 Activity by Toddalolactone as a Mechanism for Promoting Blood Circulation and Removing Stasis by Chinese Herb Zanthoxylum nitidum var. tomentosum

Zhang

Jin

et al. 2017

Front. Pharmacol.

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Traditional Chinese medicine has been used to treat a variety of human diseases for many centuries. Zanthoxylum nitidum var. tomentosum is used as an adjuvant to promote blood circulation and remove stasis. However, the mechanisms of improving circulation and other biological activities of Z. nitidum var. tomentosum are still unclear. Plasminogen activator inhibitor-1 (PAI-1) regulates the plasminogen activation system through inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA). PAI-1 has been linked to fibrin deposition that evolves into organ fibrosis and atherosclerosis. In the present study, we showed that ethanol extract prepared from Z. nitidum var. tomentosum exhibited PAI-1 inhibitory activity, and identified toddalolactone as the main active component that inhibited the activity of recombinant human PAI-1 with IC50 value of 37.31 ± 3.23 μM, as determined by chromogenic assay, and the effect was further confirmed by clot lysis assay. In vitro study showed that toddalolactone inhibited the binding between PAI-1 and uPA, and therefore prevented the formation of the PAI-1/uPA complex. Intraperitoneal injection of toddalolactone in mice significantly prolonged tail bleeding and reduced arterial thrombus weight in a FeCl3-induced thrombosis model. In addition, the hydroxyproline level in the plasma and the degree of liver fibrosis in mice were decreased after intraperitoneal injection of toddalolactone in CCl4-induced mouse liver fibrosis model. Taken together, PAI-1 inhibition exerted by toddalolactone may represent a novel molecular mechanism by which Z. nitidum var. tomentosum manifests its effect in the treatment of thrombosis and fibrosis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of PAI-1 Activity by Toddalolactone as a Mechanism for Promoting Blood Circulation and Removing Stasis by Chinese Herb Zanthoxylum nitidum var. tomentosum

Zhang

Jin

et al. 2017

Front. Pharmacol.

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“…Besides, WP-30 is a selective inhibitor to thrombin-induced platelet aggregation rather than other inducers (collagen or U46619) in vitro. 39 AEW had no effect on ADP-induced platelet aggregation in vivo in our study ( Fig. 2E).…”

Section: Discussionmentioning

confidence: 48%

“…38 A novel peptide named WP-30 from W pigra selectively inhibits thrombin-induced platelet aggregation in vitro and synthetic WP-30 attenuates thrombus formation in rats. 39 WP-30 is one kind of peptide in AEW, and it will be hydrolyzed if it is orally administered. Therefore, WP-30 was administered through tail vein to avoid hydrolyzing.…”

Section: Discussionmentioning

confidence: 99%

Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway

Yao

Liu

et al. 2020

Journal of Surgical Research

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“…As the most potent agonist of platelet activation, thrombin not only induced platelet aggregation by activating the corresponding receptors, but also promoted the development of early platelet thrombus (Adam, Guillin, & Jandrot‐Perrus, 2003; Liu et al, 2016; Maruyama, Nonaka, & Tanaka, 1993). As shown in Figure 5f, the formation of platelet thrombosis was observed.…”

Section: Resultsmentioning

confidence: 99%

The in vitro bioavailability of anti‐platelet peptides in collagen hydrolysate from silver carp ( Hypophthalmichthys molitrix ) skin

Wang

Лі

2020

J Food Biochem

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Previous animal experiments indicated collagen hydrolysates (CHs) intake decreased platelet release indicators in plasma and highlight potential applications as healthcare supplements to combat cardiovascular disease. The oligopeptides (GPR, GPRG, and GPRGP) have anti‐platelet activities. However, it is still unclear whether they are bioactive compounds in CHs from silver carp skin. We investigated the bioavailability of oligopeptides using simulated gastrointestinal digestion and Caco‐2 model. Anti‐thrombotic activities, in vitro platelet aggregation and formation of platelet thrombus, were evaluated. They resisted gastrointestinal digestion and could be absorbed by Caco‐2. Oligopeptides inhibited platelet aggregation induced by adenosine diphosphate and thrombin with IC50 of 0.160, 0.283, 0.251 mg/ml and 0.714, 1.008, 0.917 mg/ml for GPR, GPRG, and GPRGP, respectively. Oligopeptides prolonged the time of platelet thrombus and inhibited coagulation cascades, but CHs performed no bleeding side effect. These results confirmed that oligopeptides could be used as bioactive compounds of dietary supplements for pre‐thrombotic to prevent thrombosis. Practical applications Oligopeptides, GPR, GPRG, and GPRGP, derived from silver carp (Hypophthalmichthys molitrix) skin collagen, performed anti‐thrombotic activities from their anti‐platelet aggregation and anticoagulation activities. But the collagen hydrolysates containing these peptides had no side effect of bleeding in the mice model. Furthermore, this study investigated the bioavailability of these three bioactive peptides by the Caco‐2 cells model. Thus, oligopeptides GPR, GPRG, and GPRGP are a potential index of bioactive compounds in the preparation of anti‐thrombotic functional foods or healthcare supplements for people at the pre‐thrombotic state.

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A novel selective inhibitor to thrombin-induced platelet aggregation purified from the leech Whitmania pigra

Cited by 28 publications

References 27 publications

Inhibition of PAI-1 Activity by Toddalolactone as a Mechanism for Promoting Blood Circulation and Removing Stasis by Chinese Herb Zanthoxylum nitidum var. tomentosum

Inhibition of PAI-1 Activity by Toddalolactone as a Mechanism for Promoting Blood Circulation and Removing Stasis by Chinese Herb Zanthoxylum nitidum var. tomentosum

Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway

The in vitro bioavailability of anti‐platelet peptides in collagen hydrolysate from silver carp ( Hypophthalmichthys molitrix ) skin

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