Regulation of the NF-κB signaling pathway and IL-13 in asthmatic rats by aerosol inhalation of the combined active constituents of Punica granatum juice and peel.

Bronchial asthma is a chronic inflammatory airway illness. For the first time, we evaluated the proposed anti-asthmatic protective and therapeutic potency of inhaling Punica granatum juice (PJE) and peel (PPE) extract mixture (PM). Rats were challenged with ovalbumin (OVA) for 23 days and aerosolized with PM before each OVA challenge (protected group) or following the final OVA challenge for 3 days (therapeutic group). Considerable concentrations of phenolics were detected in PJE and PPE. Therefore, PM demonstrated synergistic scavenging abilities of NO and DPPH radicals. It also showed synergistic anti-inflammatory activities against lipopolysaccharide (LPS)-induced inflammation in the white blood cells by lowering the gene expression of CXCR1, CXCR2, IL-6, and IL-8. In addition, PM increased IL-10 gene expression while decreasing NO and TNF-α levels in LPS-exposed cells. Regarding the rats that were protected with PM, they exerted pulmonary pro-oxidant effects but prevented the OVA-induced upregulation of NF-κB, IKK, TNF-α, COX-2, iNOS, IL-13, and COL1A1, as well as MUC5AC and mucin over-secretion. While PM in the therapeutic group improved reactive oxygen species levels and normalized most of the investigated inflammatory and fibrotic mediators and mucin formation, but slightly improved the antioxidant indices. In addition, OVA-induced morphological alterations were massively improved after PM inhalation for short or long periods. Thus, PM inhalation prevented and treated OVA-induced pulmonary inflammation and fibrosis, while the inhalation period between 3 and 23 days needs to be optimized to acquire a better impact on the antioxidant indices.