Plant protease inhibitors compared to corticosteroids in mice with Asthma-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.