6-Gingerol, a functional polyphenol of ginger, reduces pulmonary fibrosis by activating Sirtuin1.

ABSTRACT

Pulmonary fibrosis in general is the final common outcome of various interstitial lung diseases. In recent years, the incidence of pulmonary fibrosis has been rising with poor prognosis. 6-gingerol is deemed as a functional polyphenol of ginger. The aim of the present study was to investigate the effect of 6-gingerol, on pulmonary fibrosis. Mice were randomly divided into four groups control, bleomycin, bleomycin + 6-gingerol 100 mg/kg, bleomycin + 6-gingerol 250 mg/kg, and the survival rates of the groups were recorded. Pathological and fibrotic changes in the lungs were identified by H&E and Masson staining, respectively. The levels of hydroxyproline and protein deposited in lung tissues were then, respectively, determined by colorimetry and western blotting. Subsequently, the proportion of cells and inflammatory factors in the alveolar lavage fluid were estimated. Following the identification of the possibility of Sirtuin1 (SIRT1) in the pharmacological mechanism through molecular docking and western blotting, human embryonic lung fibroblasts MRC-5 were treated with TGF-ß1 and SIRT1 inhibitor to study the role of SIRT1 in the regulatory effect of 6-gingerol. From the results, 6-gingerol was found to increase the survival rate of mice and reduce lung pathology and fibrosis in mice. And, it significantly reduced the levels of hydroxyproline and the proteins deposited in lung tissues. Moreover, the number of neutrophils, basophils, monocytes, and the levels of inflammatory factors in the alveolar lavage fluid were also reduced. SIRT1 inhibitor blocked the function of 6-gingerol to inhibit fibrosis. To sum up, 6-gingerol relieves pulmonary fibrosis via activating SIRT1. This finding expands the pharmacological effect of 6-gingerol, and it is expected to advance the development of treatments for pulmonary fibrosis.