Diammonium glycyrrhizinate inhibits histamine-induced airway smooth muscle cell activation and proliferation by regulating MAPK/FAK signal pathway and MMP-2 activity

Abstract

Excessive proliferation of airway smooth muscle cells can cause airway problems. Mast cell-derived histamine induces bronchoconstriction. Glycyrrhizic acid is used to relieve COVID-19 airway symptoms from 2020 to now, but the mechanism of action is unknown. Then diammonium glycyrrhizinate is one of the derivatives of glycyrrhizic acid, the effects of diammonium glycyrrhizinate on histamine-induced airway smooth muscle cell proliferation is not discussed yet. This study was to establish a histamine/primary rat airway smooth muscle cell model, to investigate the effects of diammonium glycyrrhizinate on these cells, and to explore the potential mechanism of diammonium glycyrrhizinate in inhibiting histamine-induced airway constriction and deep airway injury. Cell viability and proliferation were assessed; matrix metalloproteinases-2 (MMP-2) activity was examined by gelatin zymography; cell cycle was detected by flow-cytometry, protein expressions of FAK were evaluated by fluorescence-immunocytochemistry; p38, Bcl-2, PCNA and GAPDH were evaluated by western blotting. Data show that diammonium glycyrrhizinate inhibited histamine–induced airway smooth muscle cell proliferation and MMP-2 activity; recovers histamine-induced airway smooth muscle cell cycle disorders, and restores the histamine-regulated intracellular signals. The present study suggests an underlying mechanism that diammonium glycyrrhizinate can relieve the airway symptom of COVID-19 patients by inhibiting histamine-induced over-activation/proliferation and regulating airway smooth muscle cell intracellular signaling pathways. The pharmaceutical potential of diammonium glycyrrhizinate requires attention.