Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-β1 and iNOS

Naunyn Schmiedebergs Arch Pharmacol. 2020 Sep;393(9):1659-1670. doi: 10.1007/s00210-020-01881-7. Epub 2020 May 6.

Abstract

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger (Zingiber officinale L.) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson's trichrome staining. Transforming growth factor-beta 1 (TGF-β1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-α and IL-1β levels, MDA level, TGF-β1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-β1 and iNOS signaling pathways.

Keywords: Antifibrotic effect; Inducible nitric oxide synthase (iNOS); Pulmonary fibrosis; Transforming growth factor-beta 1 (TGF-β1); Zingerone.