Antioxidant and Anti-Inflammatory Effects of Glycyrrhizin Against LPS-Induced Pulmonary Inflammation in A-549 Cells Through Modulation of Oxidative Stress and Inflammatory Signalling

Abstract

Acute lung injury (ALI) is a severe and potentially fatal inflammatory condition characterized by heightened oxidative stress and the overproduction of pro-inflammatory cytokines. The present study explores the protective role of glycyrrhizin, a principal bioactive compound derived from Glycyrrhiza glabra, in mitigating lipopolysaccharide (LPS)-induced lung epithelial damage in A-549 cells. Exposure to LPS significantly compromised cell viability and led to a pronounced increase in intracellular reactive oxygen species (ROS) and inflammatory mediators such as TNF-α, IL-1β, and IL-6. Pre-treatment with glycyrrhizin effectively restored cell viability in a dose-dependent manner and substantially reduced ROS accumulation. Enzyme-linked immunosorbent assay (ELISA) and Western blot analyses demonstrated that glycyrrhizin downregulated the expression of critical pro-inflammatory markers, including NF-κB p65, IL-1β, and components of the NLRP3 inflammasome complex—namely NLRP3, ASC, and Caspase-1. These protein-level observations were further supported by qRT-PCR results, which showed decreased mRNA expression of NF-κB p65, NLRP3, Caspase-1, and IL-1β. Importantly, glycyrrhizin counteracted LPS-induced degradation of IκB-α and inhibited the nuclear translocation of NF-κB, suggesting suppression of the classical NF-κB signaling pathway. This dual inhibition of NF-κB activation and NLRP3 inflammasome assembly underscores glycyrrhizin’s mechanistic potential in attenuating the inflammatory cascade associated with ALI. In conclusion, the findings indicate that glycyrrhizin exerts significant anti-inflammatory and antioxidant effects in vitro, supporting its potential as a therapeutic agent for respiratory inflammatory conditions such as acute lung injury. These promising outcomes justify further exploration in animal models to establish its protective efficacy and pave the way for potential clinical application