Echinacea purpurea ameliorates Bleomycin-induced pulmonary fibrosis in rats through modulating NADPH oxidase-4 and endothelin-1/connective tissue growth factor/matrix metalloproteinases signalling axis

Abstract

Abstract Idiopathic pulmonary fibrosis (IPF) is one of the rapidly progressing interstitial lung illnesses. Bleomycin (Bleo) is used as a chemotherapeutic agent for the treatment of lymphoma patients. The major side effects of Bleo include lung fibrosis, characterized by the accumulation of inflammatory cells. Echinacea purpurea (ECH) possesses immune-modulating, antiviral, antimicrobial and anti-inflammatory activities. The current study aims to evaluate the possible protective effects of ECH against Bleomycin-induced pulmonary fibrosis. Forty rats were divided into four groups (n = 10). Group I represented the normal-control group. Group II represented the Bleo-control group. Groups III and IV received intra-tracheal Bleo followed by oral ECH (25 and 50 mg/kg); respectively, for 1 month. Lung tissue contents of reduced glutathione (GSH), malondialdehyde (MDA), transforming growth factor-beta (TGF-β), matrix metalloproteinases (MMP-2 & MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), MMP-9/TIMP-1 ratio, collagen-1 and alpha-Smooth muscle actin (α-SMA) were measured. NADPH oxidase 4 (NOX4), connective tissue growth factor (CTGF) and endothelin-1 (ET-1) genes were quantified using PCR. Moreover, lung tissue histopathological changes were screened. Intra-tracheal Bleo instillation resulted in significant increments in the lung tissue contents of MDA, TGF-β, MMP-2 & MMP-9, TIMP-1, MMP-9/TIMP-1 ratio, collagen-1 and α-SMA. Moreover, Bleo significantly elevated the PCR expression of NOX4, CTGF and ET-1 genes in lung tissues and caused apparent lung tissue histopathological fibrotic changes. ECH treatment ameliorated all the aforementioned parameters and mitigated the lung tissue histopathological fibrotic changes induced by Bleo. The study highlighted for the first time the anti-oxidant, anti-inflammatory and anti-fibrotic effects of ECH against Bleo-induced pulmonary fibrosis in rats. The study suggests that these effects are mainly mediated via the modulation of Gelatinases, NOX4, ET-1 and CTGF. Accordingly, ECH is anticipated as a potential therapy to be added to the treatment regimen of pulmonary fibrosis.