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Planta Med 2021; 87(01/02): 169-176
DOI: 10.1055/a-1202-4799
Biological and Pharmacological Activities
Original Papers

Bauhinia Protease Inhibitors Attenuate Gastric Ulcer by Blocking Neutrophil Enzymes

Mayara Vioto Valois
1   Department of Biochemistry, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil
,
Cleide de Oliveira
1   Department of Biochemistry, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil
,
Antonio José Lapa
2   Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil
3   Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil
,
Caden Souccar
2   Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil
,
Maria Luiza Vilela Oliva 
1   Department of Biochemistry, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil
› Author AffiliationsSupported by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Finance Code 001
Supported by: Fundação de Amparo à Pesquisa do Estado de São Paulo 72017/06630-2017/07972-9
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 401452/2016-6
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 406542/2013-9
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Abstract

Proteases play a pivotal role in many signaling pathways; inhibitors of well-established proteases have shown a substantial therapeutic success. This study aimed to examine the in vivo effects of 3 protease inhibitors isolated from Bauhinia species: i) Bauhinia mollis elastase inhibitor, which blocks human neutrophil elastase (Kiapp 2.8 nM) and cathepsin G (Kiapp 1.0 nM) activities; ii) Bauhinia mollis trypsin inhibitor, a trypsin inhibitor (Kiapp 5.0 nM); and iii) Bauhinia bauhinioides cruzipain inhibitor, which inhibits elastase (Kiapp 2.6 nM), cathepsin G (Kiapp 160.0 nM), and the cysteine proteases cathepsin L (Kiapp 0.2 nM). Bauhinia bauhinioides cruzipain inhibitor, Bauhinia mollis elastase inhibitor, and Bauhinia mollis trypsin inhibitor were isolated using acetone and ammonium sulfate fractionations, DEAE-Sephadex, trypsin-Sepharose, and Resource-Q chromatographies. Mice and rats were treated intraperitoneally with 1 dose of inhibitor; gastric mucosal lesions were induced by cold-restraint stress. Oral pretreatment of mice with Bauhinia mollis elastase inhibitor or Bauhinia mollis trypsin inhibitor (1 – 10 mg/kg) did not show anti-ulcer effect, while Bauhinia bauhinioides cruzipain inhibitor (0.1 – 1.0 mg/kg) produced a similar reduction of the index of mucosal damage at all effective doses (30 to 33% < control). In rats at doses lower than those used in mice, Bauhinia mollis elastase inhibitor and Bauhinia bauhinioides cruzipain inhibitor reduced the index of mucosal damage by 66% and 54% of controls, respectively. The results indicate a protective effect against gastric mucosal lesions associated with elastase inhibition but not inhibition of trypsin activities. Moreover, the lack of Bauhinia mollis elastase inhibitor efficacy observed in mice may possibly be related to the reported structural differences of elastase in mice and rats.

Key words

Bauhinia bauhiniodes - Bauhinia mollis - elastase - gastric mucosal lesions - Leguminosae - protease inhibitor

Supporting Information

    Isolation of Bauhinia mollis elastase inhibitor (BmEI) and Bauhinia mollis trypsin inhibitor (BmTI).

  • Supporting Information


Publication History

Received: 09 April 2020

Accepted after revision: 13 June 2020

Article published online:
14 July 2020

© 2020. Thieme. All rights reserved.

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