Effects of a Peptide Derived from the Primary Sequence of a Kallikrein Inhibitor Isolated from Bauhinia bauhinioides (pep-BbKI) in an Asthma-COPD Overlap (ACO) Model

Int J Mol Sci. 2023 Jul 9;24(14):11261. doi: 10.3390/ijms241411261.

Abstract

(1) There are several patients with asthma-COPD overlap (ACO). A peptide derived from the primary sequence of a kallikrein inhibitor isolated from Bauhinia bauhinioides (pep-BbKI) has potent anti-inflammatory and antioxidant effects. Purpose: To investigate the effects of pep-BbKI treatment in an ACO model and compare them with those of corticosteroids. (2) BALB/c mice were divided into groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep-BbKI (treated with inhibitor), ACO-DX (dexamethasone treatment), ACO-DX-pep-BbKI (both treatments), and SAL-pep-BbKI (saline group treated with inhibitor). We evaluated: hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), exhaled nitric oxide (eNO), IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, MMP-9, MMP-12, TGF-β, collagen fibers, iNOS, eNO, linear mean intercept (Lm), and NF-κB in airways (AW) and alveolar septa (AS). (3) ACO-pep-BbKI reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, neutrophils, IL-5, IL-10, IL-17, IFN-γ, TNF-α, MMP-12 (AW), collagen fibers, iNOS (AW), and eNO (p > 0.05). ACO-DX reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, total cells and differentials, IL-1β(AS), IL-5 (AS), IL-6 (AS), IL-10 (AS), IL-13 (AS), IFN-γ, MMP-12 (AS), TGF-β (AS), collagen fibers (AW), iNOS, and eNO (p > 0.05). SAL was similar to SAL-pep-BbKI for all comparisons (p > 0.05). (4) Pep-BbKI was similar to dexamethasone in reducing the majority of alterations of this ACO model.

Keywords: ACO; Bauhinia; airway remodeling; inflammation; oxidative stress; serine proteinase inhibitors.

MeSH terms

  • Animals
  • Asthma* / drug therapy
  • Bauhinia*
  • Bronchoalveolar Lavage Fluid
  • Collagen
  • Dexamethasone
  • Disease Models, Animal
  • Interleukin-10
  • Interleukin-13
  • Interleukin-17
  • Interleukin-5
  • Interleukin-6
  • Kallikreins
  • Matrix Metalloproteinase 12
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Pancreatic Elastase
  • Peptides / pharmacology
  • Plant Proteins / pharmacology
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Tumor Necrosis Factor-alpha

Substances

  • Interleukin-10
  • Interleukin-17
  • Ovalbumin
  • Interleukin-13
  • Interleukin-5
  • Interleukin-6
  • Matrix Metalloproteinase 12
  • Tumor Necrosis Factor-alpha
  • Plant Proteins
  • Peptides
  • Kallikreins
  • Pancreatic Elastase
  • Dexamethasone
  • Collagen