Dipotassium Glycyrrhizinate Against Fibrotic Effects of Histamine Depletes Intracellular Glutathione to Discomfort Mitochondrial, Inducing Cell Apoptosis/ Ferroptosis of Over-Activated Lung Fibroblast

Abstract

Pulmonary fibrosis (PF) is the common outcome of a variety of chronic lung diseases and systemic diseases, and the consequence of Coronavirus Disease 2019 (COVID-19). There is currently a lack of effective treatments to reverse this disease or prevent its development. The purpose of this study is to investigate the effect of dipotassium glycyrrhizinate (DG) on lung fibroblasts and the possible mechanism of alleviating pulmonary fibrosis. Extract primary lung fibroblasts, establish cell models, and use time-lapse photography to continuously monitor the effects of dipotassium glycyrrhizinate and histamine on the morphology of lung fibroblasts. The content of glutathione in cells was detected by the fluorescence method. Cell mitochondrial membrane potential was examined, protein expressions of P53, Caspase-3, Bax and Bal-2 of lung fibroblasts were evaluated by western blot and immune cytochemistry. Our data demonstrated that dipotassium glycyrrhizinate inhibited histamine-induced cell growth/proliferation, glutathione content, mitochondrial membrane potential; also down-regulated P53 and up-regulated the ratio of Bax/Bcl-2, leading to the ferritosis/apoptosis of activated lung fibroblasts, against the fibrotic effects of histamine. Present study provided a new pharmaceutics mechanism of dipotassium glycyrrhizinate for the treatment of lung fibrosis that dipotassium glycyrrhizinate against fibrotic effects of histamine depletes intracellular glutathione to discomfort mitochondrial, inducing cell apoptosis/ferroptosis of over-activated lung fibroblast.