The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models

Brito, Marlon Vilela de; Oliveira, Cristino Carneiro; Salu, Bruno Ramos; Andrade, Sofia; Malloy, Paula M. D.; Sato, Ana Claudia; Vicente, Cristina Pontes; Sampaio, Misako U.; Maffei, Francisco Humberto de Abreu; Oliva, Maria Luíza Vilela

doi:10.1016/j.thromres.2014.02.027

Cited by 22 publications

(18 citation statements)

References 50 publications

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“…rBbKI strongly inhibits the activity of trypsin, plasmin, and HuPk (human plasma kallikrein). The inhibition of human plasma kallikrein activity by rBbKI causes a decreased release of bradykinin by decreasing the availability of HuPK [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…All doses were administered two hours after porcine pancreatic elastase instillation ( Figure 2 ). This dose was determined in the previous studies of Brito et al [ 18 ] which showed that this is the dose required to extrapolate the amount necessary for complete inhibition of circulating plasma kallikrein and no toxic effects was observed in the experimental model.…”

Section: Methodsmentioning

confidence: 99%

“…Inhibition of HuPK by BbKI/rBbKI causes a decrease in bradykinin release due to the decreased availability of HuPK. BbKI is the first plant-derived inhibitor of the primary structure set described that is an inhibitor of tissue kallikrein [ 17 , 18 ]. Indeed, rBbKI was effective in inhibiting the viability of tumor cell lines [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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The Plant-DerivedBauhinia bauhinioidesKallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice

Martins-Olivera

Almeida-Reis

Theodoro-Junior

et al. 2016

Mediators of Inflammation

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Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD). However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI) to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group) or saline (SAL group) and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups). At day 28, the following analyses were performed: (I) lung mechanics, (II) exhaled nitric oxide (ENO), (III) bronchoalveolar lavage fluid (BALF), and (IV) lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The Plant-DerivedBauhinia bauhinioidesKallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice

Martins-Olivera

Almeida-Reis

Theodoro-Junior

et al. 2016

Mediators of Inflammation

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“…37,38 Similarly, other plasma kallikrein inhibitors have also shown to have antithrombotic properties in vitro or in animal models of venous and arterial thrombosis ( Table 1). [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] These studies provide strong evidence that although components of the plasma KKS are dispensable for normal hemostasis, they play a central role in pathological thrombus formation.…”

Section: Plasma Kallikrein: Synthesis Structure and Functionsmentioning

confidence: 99%

Plasma Kallikrein Inhibitors in Cardiovascular Disease

Kolte

Shariat‐Madar

2016

Cardiology in Review

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Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine protease plasma kallikrein, and circulates in plasma bound to high molecular weight kininogen. Plasma prekallikrein is activated to plasma kallikrein by activated factor XII or prolylcarboxypeptidase. Plasma kallikrein regulates the activity of multiple proteolytic cascades in the cardiovascular system such as the intrinsic pathway of coagulation, the kallikrein-kinin system, the fibrinolytic system, the renin-angiotensin system, and the complement pathways. As such, plasma kallikrein plays a central role in the pathogenesis of thrombosis, inflammation, and blood pressure regulation. Under physiological conditions, plasma kallikrein serves as a cardioprotective enzyme. However, its increased plasma concentration or hyperactivity perpetuates cardiovascular disease (CVD). In this article, we review the biochemistry and cell biology of plasma kallikrein and summarize data from preclinical and clinical studies that have established important functions of this serine protease in CVD states. Finally, we propose plasma kallikrein inhibitors as a novel class of drugs with potential therapeutic applications in the treatment of CVDs.

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“…Legumes in the genus Bauhinia (Caesalpinoideae) are widely distributed in most of the tropical regions worldwide including Africa, Asia and South America (Cechinel Filho, 2009). Many biological activities have been identified in compounds from Bauhinia bauhinioides (BBL), being one of the most studied antithrombotic and antitumor effects resulting from the action of kallikrein isolated from this bean (Brito et al, 2014;Bilgin et al, 2014). Another important substance extracted from BBL is a sugar-binding protein, denominated lectin.…”

Section: Introductionmentioning

confidence: 99%

The galactose‐binding lectin isolated from Bauhinia bauhinioides Mart seeds inhibits neutrophil rolling and adhesion via primary cytokines

Girão

Cavada

Pires

et al. 2015

J of Molecular Recognition

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In this study, the amino acid sequence and anti-inflammatory effect of Bauhinia bauhinioides (BBL) lectin were evaluated. Tandem mass spectrometry revealed that BBL possesses 86 amino acid residues. BBL (1 mg/kg) intravenously injected in rats 30 min prior to inflammatory stimuli inhibited the cellular edema induced by carrageenan in only the second phase (21% - 3 h, 19% - 4 h) and did not alter the osmotic edema induced by dextran. BBL also inhibited carrageenan peritoneal neutrophil migration (51%), leukocyte rolling (58%) and adhesion (68%) and the neutrophil migration induced by TNF-α (64%). These effects were reversed by the association of BBL with galactose, demonstrating that the carbohydrate-binding domain is essential for lectin activity. In addition, BBL reduced myeloperoxidase activity (84%) and TNF-α (68%) and IL1-β (47%) levels. In conclusion, the present investigation demonstrated that BBL contains highly homologous isolectins, resulting in a total of 86 amino acid residues, and exhibits anti-inflammatory activity by inhibiting neutrophil migration by reducing TNF-α and IL1-β levels via the lectin domain.

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The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models

Cited by 22 publications

References 50 publications

The Plant-DerivedBauhinia bauhinioidesKallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice

The Plant-DerivedBauhinia bauhinioidesKallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice

Plasma Kallikrein Inhibitors in Cardiovascular Disease

The galactose‐binding lectin isolated from Bauhinia bauhinioides Mart seeds inhibits neutrophil rolling and adhesion via primary cytokines

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