Chelerythrine Ameliorates Pulmonary Fibrosis via Activating the Nrf2/ARE Signaling Pathway.

Abstract

Chelerythrine (CHE) is a natural benzophenanthridine alkaloid, which has shown its anti-fibrosis activity in kidney and liver, while the impact of CHE in pulmonary fibrosis is still unclear. This study is developed to explore the impact and mechanism of CHE in pulmonary fibrosis. Pulmonary fibrosis mouse models were established through intratracheal injection of bleomycin (BLM), after which the mice were intraperitoneally injected with CHE (0.375 or 0.75 mg/kg/d) every other day. The mice were sacrificed at the 28th day to collect blood serum, bronchoalveolar lavage fluid (BALF), and pulmonary tissues. Then, the severity of pulmonary fibrosis and the expression of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2) in the pulmonary tissues were detected. Western blot analysis quantified the expressions of fibronectin and alpha-smooth muscle actin (α-SMA). The levels of 4-hydroxynonenal (4-HNE), glutathione (GSH), superoxide dismutase (SOD), TGF-β and hydroxyproline (HP) in the BALF, and pulmonary tissues were measured. The expression levels of Nrf2 and its downstream genes, hemeoxygenase-1 (HO-1) and NAD (P) H: quinone oxidoreductase (NQO1) were examined. CHE at the concentration of 0.375 or 0.75 mg/kg/d could attenuate pulmonary fibrosis. CHE injection reduced the expression levels of fibronectin, α-SMA, and TGF-β, upregulated the levels of SOD and GSH and decreased the levels of 4-HNE and HP. Also, CHE increased the expressions of Nrf2, HO-1, and NQO1. Treatment of Nrf2/antioxidant response element (ARE) inhibitor could block the Nrf2/ARE signaling pathway, thus perturbing the inhibition of CHE on BLM-stimulated pulmonary fibrosis in mice. CHE alleviates BLM-induced pulmonary fibrosis in mice through activating the Nrf2/ARE pathway to increase the activity of antioxidant enzymes.