Bauhinia Protease Inhibitors Attenuate Gastric Ulcer by Blocking Neutrophil Enzymes

Author(s)

Valois, Mayara Vioto ^[1] ; de Oliveira, Cleide ^[1] ; Lapa, Antonio Jose ^{[2, 3]} ; Souccar, Caden ^[3] ; Vilela Oliva, Maria Luiza ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Sao Paulo, SP - Brazil

^[2] Univ Estado Amazonas, Manaus, Amazonas - Brazil

^[3] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Planta Medica; v. 87, n. 01/02, p. 169-176, FEB 2021.
• Web of Science Citations: 0

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 (Ki (app) 2.8nM) and cathepsin G (Ki (app) 1.0nM) activities; ii) Bauhinia mollis trypsin inhibitor, a trypsin inhibitor (Ki (app) 5.0nM); and iii) Bauhinia bauhinioides cruzipain inhibitor, which inhibits elastase (Ki (app) 2.6nM), cathepsin G (Ki (app) 160.0nM), and the cysteine proteases cathepsin L (Ki (app) 0.2nM). 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 (1-10mg/kg) did not show anti-ulcer effect, while Bauhinia bauhinioides cruzipain inhibitor (0.1-1.0mg/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. (AU)

• FAPESP's process: 17/07972-9 - Development of lead agents for prophylaxis and treatment of cardiovascular diseases
• Grantee: Maria Luiza Vilela Oliva
• Support Opportunities: Regular Research Grants