Inibidor de serinoproteinase obtido de sementes de Juquiri (Mimosa regnelli Benth.) com atividade anti-inflamatória, anticoagulante e adjuvante da heparina
Hemostasis is the event that mammals use to block the loss of blood and promote injury repair, and failure by overeating contributes to the spread of inflammatory and thrombotic factors. Atherosclerosis is an example of such diseases, and heparin (Hep) is a treatment drug. Patients with antithrom...
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מחברים אחרים: | |
פורמט: | Dissertação |
שפה: | por |
יצא לאור: |
Brasil
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נושאים: | |
גישה מקוונת: | https://repositorio.ufrn.br/jspui/handle/123456789/25528 |
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סיכום: | Hemostasis is the event that mammals use to block the loss of blood and promote
injury repair, and failure by overeating contributes to the spread of inflammatory and
thrombotic factors. Atherosclerosis is an example of such diseases, and heparin
(Hep) is a treatment drug. Patients with antithrombin deficiency have resistance to
the anticoagulant effects of Hep, so researches for novel homeostatic molecules that
contribute to clinical treatments are necessary. Plant protease inhibitors have been
effective in controlling biological processes, such as coagulation and inflammation.
The present work aimed isolate a trypsin inhibitor from the Juquiri (JTI) seed and
evaluate its activity against serine proteases, and its anticoagulant and antiinflammatory
potentials. JTI was isolated by affinity and ion exchange
chromatography, presenting two major protein bands of 11.9 and 19.2 kDa on SDSPAGE,
and was able to inhibit trypsin and chymotrypsin. In coagulation, JTI
prolonged partial thromboplastin time (APTT) at concentrations greater than 2 μg/100
μL plasma, without prolonging prothrombin time (PT). Associated with Hep, JTI was
able to enhance the anticoagulant effect of the drug in both tests. Without toxicity to
human erythrocytes, JTI reduced 40% of elastase concentrations released by
neutrophils induced by platelet activating factor (PAF). JTI at concentrations between
20-80 μg/mL stimulated TNF production by macrophages (RAW 264.7) in culture
without provoking other inflammatory stimuli. LPS-activated macrophages had a
reduction in NO, IL-6 and TNF productions when treated with JTI at 20-160 μg/mL
concentrations. These data point to JTI as promising in the treatment of thrombotic
and inflammatory diseases and have been effective as heparin adjuvant and to
promote the reduction of neutrophil inflammatory stimuli likely by MAPK-dependent
pathways and in macrophages by NF-κB transcription factor pathways. |
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