Bauhinia Protease Inhibitors Attenuate Gastric Ulcer by Blocking Neutrophil Enzymes.

Autor: Valois MV; Department of Biochemistry, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil., de Oliveira C; Department of Biochemistry, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil., Lapa AJ; Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil.; Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil., Souccar C; Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil., Oliva MLV; Department of Biochemistry, Universidade Federal de São Paulo, Escola Paulista de Medicina, SP, Brazil.
Jazyk: angličtina
Zdroj: Planta medica [Planta Med] 2021 Feb; Vol. 87 (1-02), pp. 169-176. Date of Electronic Publication: 2020 Jul 14.
DOI: 10.1055/a-1202-4799
Abstrakt: 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 (Ki app  2.8 nM) and cathepsin G (Ki app  1.0 nM) activities; ii) Bauhinia mollis trypsin inhibitor, a trypsin inhibitor (Ki app  5.0 nM); and iii) Bauhinia bauhinioides cruzipain inhibitor, which inhibits elastase (Ki app  2.6 nM), cathepsin G (Ki app  160.0 nM), and the cysteine proteases cathepsin L (Ki app  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.
Competing Interests: The authors declare that they have no conflict of interest.
(Thieme. All rights reserved.)
Databáze: MEDLINE
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