(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.

The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma–COPD overlap—ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-β), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t-tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-β, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1β, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-β, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.

Background: Plant protease inhibitors have anti-inflammatory activities and represent potential treatment for inflammatory diseases. Aims: To investigate the effects of Enterolobium contortisiliquum Tissue Inhibitor(EcTI), Bauhinia bauhinioides Kallikrein Inhibitor(BbKI) and fraction of BbKI(BbKIm) compared to dexamethasone(DX) treatment in a model of asthma-COPD. Methods: Balb/c mice were divided in groups(n=8): SAL, OVA (OV), ELA, OV+ELA, OV+ELA-EcTI, OV+ELA-BbKI, OV+ELA-BbKIm and OV+ELA-DX. After day 29, we evaluated resistance (Rrs) and elastance (Ers) of respiratory system, exhaled nitric oxide (ENO), and total cells in bronchoalveolar lavage fluid (BALF). Results: %Ers decreased in OV+ELA and ELA compared to OVA (p<0.05). OV+ELA-EcTI (186.7±39.5%), OV+ELA-BbKI (260.7±31.5%), OV+ELA-BbKIm (159.6±76.9%) and OV+ELA-DX (227.3±70.4%) decreased %Rrs compared to OV+ELA (625.1±81.0%). %Ers in OV+ELA-EcTI (118.9±28.1%), OV+ELA-BbKI (110.3±28.1%), OV+ELA-BbKIm (41.9±10.2%) and OV+ELA-DX (112.5±19.7%) increased compared to OV+ELA (36.4±4.8% p<0.05). ENO (expressed as ppb) in OV+ELA-EcTI (16.6±2.2), OV+ELA-BbKI (6.6±0.8), OV+ELA-BbKIm (9.3±2.8) and OV+ELA-DX (20.0±3.5) decreased compared to OV+ELA (41.0±5.1) (p<0.05). BALF total cells (expressed as -x10⁴cells/mL) in OV+ELA-EcTI (5.4±1.0), OV+ELA-BbKI (9.4±2.2), OV+ELA-BbKIm (7.0±1.5) and OV+ELA-DX (2.5±02) decreased compared to OV+ELA (23.2±2.9, p<0.05). There were no difference among OV+ELA-EcTI, OV+ELA-BbKI, OV+ELA-BbKIm & OV+ELA-DX in all comparisons. Conclusions: EcTI, BbKI and BbKIm were similar to corticosteroids in controlling lung mechanics and inflammation in this asthma-COPD model. Financial Support: FAPESP (2018/02537-5), CNPq, LIM20HCFMUSP.